Spatiotemporal and geometric optimization of sensor arrays for detecting analytes fluids

ABSTRACT

Sensor arrays and sensor array systems for detecting analytes in fluids. Sensors configured to generate a response upon introduction of a fluid containing one or more analytes can be located on one or more surfaces relative to one or more fluid channels in an array. Fluid channels can take the form of pores or holes in a substrate material. Fluid channels can be formed between one or more substrate plates. Sensor can be fabricated with substantially optimized sensor volumes to generate a response having a substantially maximized signal to noise ratio upon introduction of a fluid containing one or more target analytes. Methods of fabricating and using such sensor arrays and systems are also disclosed.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation-in-part of U.S. applicationSer. No. 09/568,784, filed on May 10, 2000, which claims the benefit ofU.S. Provisional Application No. 60/133,318, filed on May 10, 1999, U.S.Provisional Application No. 60/140,027, filed on Jun. 16, 1999. Thisapplication also claims the benefit of U.S. Provisional Application No.60/199,221, filed on Apr. 24, 2000, and U.S. Provisional Application No.60/235,385, filed on Sep. 25, 2000. All of these prior applications andprovisional applications are incorporated by reference herein.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

[0002] The U.S. Government has certain rights in this invention pursuantto Grant Nos. DAAK-60-97-K-9503 administered by the Defense AdvancedResearch Projects Agency, DAAG55-97-1-0187 and DAAG55-98-1-0266, bothadministered by the United States Army, DE-FG03-98NV13367 administeredby the Department of Energy, and NAS-1407 administered by the NationalAeronautics and Space Administration.

FIELD OF THE INVENTION

[0003] This invention relates generally to sensors and sensor systemsfor detecting analytes in fluids and, more particularly, to sensorsystems that incorporate sensors having electrical properties that varyaccording to the presence and concentration of analytes, and to methodsof using such sensor systems.

BACKGROUND

[0004] There is considerable interest in developing sensors that act asanalogs of the mammalian olfactory system (Lundstrom et al. (1991)Nature 352:47-50; Shurmer and Gardner (1992) Sens. Act. B 8:1-11;Shurmer and Gardner (1993) Sens. Actuators B 15:32). Prior attempts toproduce broadly responsive sensor arrays have exploited heated metaloxide thin film resistors (Gardner et al. (1991) Sens. Act. B4:117-121;Gardner et al. (1991) Sens. Act. B 6:71-75), polymer sorption layers onthe surfaces of acoustic wave (SAW) resonators (Grate and Abraham (1991)Sens. Act. B 3:85-111; Grate et al. (1993) Anal. Chem. 65:1868-1881),arrays of electrochemical detectors (Stetter et al. (1986) Anal. Chem.58:860-866; Stetter et al. (1990) Sens. Act. B 1:43-47; Stetter et al.(1993) Anal. Chem. Acta 284:1-11), conductive polymers or compositesthat consist of regions of conductors and regions of insulating organicmaterials (Pearce et al. (1993) Analyst 118:371-377; Shurmer et al.(1991) Sens. Act. B 4:29-33; Doleman et al. (1998) Anal. Chem.70:2560-2654; Lonergan et al. Chem. Mater. 1996, 8:2298). Arrays ofmetal oxide thin film resistors, typically based on tin oxide (SnO2)films that have been coated with various catalysts, yield distinct,diagnostic responses for several vapors (Corcoran et al. (1993) Sens.Act. B 15:32-37). Surface acoustic wave resonators are extremelysensitive to both mass and acoustic impedance changes of the coatings inarray elements, but the signal transduction mechanism involves somewhatcomplicated electronics, requiring frequency measurement to 1 Hz whilesustaining a 100 MHZ Rayleigh wave in the crystal. Attempts have alsobeen made to construct arrays of sensors with conducting organic polymerelements that have been grown electrochemically through use of nominallyidentical polymer films and coatings. Moreover, Pearce et al., (1993)Analyst 118:371-377, and Gardner et al., (1994) Sensors and Actuators B18-19:240-243 describe, polypyrrole based sensor arrays for monitoringbeer flavor. U.S. Pat. No. 4,907,441, describes general sensor arrayswith particular electrical circuitry. U.S. Pat. No. 4,674,320 describesa single chemoresistive sensor having a semi-conductive materialselected from the group consisting of phthalocyanine, halogenatedphthalocyanine and sulfonated phthalocyanine, which was used to detect agas contaminant. Other gas sensors have been described by Dogan et al.,Synth. Met. 60, 27-30 (1993) and Kukla, et al. Films. Sens. Act. B.,Chemical 37, 135-140 (1996).

[0005] Typically, the detectors in such an array are placed in nominallyspatially equivalent positions relative to the analyte flow path. Insuch a configuration, any spatiotemporal differences between detectorsare minimized, and the array response pattern is determined by thediffering physicochemical responses of the various detectors towards theanalyte of interest. The variations in analyte sorption amongst variousdetectors thus determines the resolving power of the detector array anddetermines the other performance parameters of such systems.

[0006] Additionally, the form factor of the individual detectors in sucharrays is typically constrained by factors related to the mode of signaltransduction. For example, most film-coated quartz-crystal microbalance(QCM) devices must have specified dimensions so that a resonant bulkacoustic wave can be maintained in the quartz crystal transducerelement. Similarly, the geometry of SAW devices is constrained by theneed to sustain a Rayleigh wave of the appropriate resonant frequency atthe surface of the transducer crystal. Each detector in a QCM or SAWarray typically has an identical area and form factor; consequently, thearray response is based solely on the different polymer/analyte sorptionproperties of the differing detector films.

[0007] In practice, most chemical sensors suffer from problemsassociated with mass transport of the analyte to be detected to thesensor regardless of the type of detector or sensor.

SUMMARY OF THE INVENTION

[0008] The invention provides apparatus, systems and methods fordetecting the presence of analytes in fluids. Sensor arrays incorporatemultiple sensors or detectors. To optimize transport of gaseous analytesto these sensors, sensor arrays can incorporate multiple holes, pores orchannels, thus increasing analyte flux.

[0009] The geometry and spatiotemporal location of individual detectorscan be optimized based on analyte characteristics, such as polymer/gaspartition coefficients. For analytes with moderate polymer/gas partitioncoefficients, detector signal-to-noise can optimized for detectors ofvery large area. For analytes with high polymer/gas partitioncoefficients, detectors of small area will exhibit optimum vapordetection sensitivity. Manipulation of the geometric form factor ofdetectors can provide a convenient method for optimizing the S/Nperformance for a particular detector/analyte combination of interest.An array of nominally identical sorption detectors arranged linearlyrelative to the analyte flow path can produce different spatiotemporalresponse patterns for analytes having different polymer/gas partitioncoefficients. Analytes with moderate polymer/gas partition coefficientscan produce the same signals on all detectors over a range of flowrates, whereas analytes with very large polymer/gas partitioncoefficients can produce signals that are highly dependent on theanalyte flow rate and the spatial position of the detector in the array.Such a configuration can produce useful information on the compositionof binary analyte mixtures and adds classification information to anarray of compositionally different vapor detectors.

[0010] In general, in one aspect, the invention features flow-throughsystems for detecting an analyte in a fluid flow. The systems include asensor array having a first face and a second face, a fluid flow systemfor introducing a fluid flow containing an analyte to the sensor array,such that upon introduction of a fluid flow to the sensor array apressure differential is created between the first and second faces ofthe sensor array, and a processor configured to receive the responsegenerated by the one or more first sensors and to process the responseto detect at least one analyte in a fluid flow. The sensor arrayincludes one or more first sensors and one or more fluid channelsextending from the first face to the second face. At least one of thefirst sensors is located at a first position in the sensor array incontact with the first face of the sensor array. The sensors areconfigured to generate a response upon exposure of the sensor array toat least one analyte in a fluid flow.

[0011] Particular implementations of the invention can include one ormore of the following features. The sensor array can include a substratehaving a first surface and a second surface. The fluid channels canextend from the first surface to the second surface. The fluid channelscan include a plurality of pores in a microporous substrate material, ora plurality of holes introduced into an impermeable substrate material.The fluid flow system can include a predetermined sampling volume, withthe sensor array located within the sampling volume. The first sensorcan have a sensor volume substantially optimized to cause the firstsensor to generate a response having a maximum signal to noise ratio forat least one target analyte. The sensor volume can be substantiallyoptimized as a function of a partition coefficient K of at least onetarget analyte. The predetermined sampling volume can include aheadspace proximate to the first sensor, the headspace having aheadspace volume V_(l). The sensor volume V_(p) can be substantiallyoptimized based on the function V_(p)=V_(l)/K. The first sensors caninclude one, or multiple, vapor sensors for detecting an analyte in agas. The first sensors can include one, or multiple, liquid sensors fordetecting an analyte in a liquid.

[0012] The sensor array can include at least one second sensor locatedat a second position in the sensor array. The second position can bedifferent from the first position relative to the fluid flow. The firstand second sensors can each generate a response upon exposure of thesensor array to at least one analyte in a fluid flow, such that theresponses generated upon exposure of the sensor array to at least oneanalyte in a fluid flow include a spatio-temporal difference between theresponses for the first and second sensors. The processor can beconfigured to resolve a plurality of analytes in a fluid flow uponexposure of the sensor array to a fluid flow containing the plurality ofanalytes. The sensor array can include a plurality of second sensors.Each of the first sensor and a plurality of the second sensors can belocated at a different position in the sensor array relative to thefluid flow. The first and second sensors can each generate a responseupon exposure of the sensor array to at least one analyte in a fluidflow, such that the responses generated upon exposure of the sensorarray to at least one analyte in a fluid flow include a spatio-temporaldifference between the responses for the first and second sensors.

[0013] The sensor array can include a first substrate forming a platehaving a length, a width, and a depth, such that the length and thewidth in combination define a pair of substrate faces and the width andthe depth in combination define a pair of substrate edges. The firstsubstrate can be oriented in the sampling volume such that the substratefaces extend in a direction parallel to a direction of the fluid flowand the substrate edges are situated normal to the fluid flow. The firstsensors can be located on one of the pair of substrate edges. The sensorarray can include one or more second sensors located on one of the pairof substrate faces.

[0014] The processor can be configured to resolve a plurality ofanalytes in a fluid flow upon exposure of the sensor array to a fluidflow containing the plurality of analytes. The sensor array can includea plurality of second sensors located at different positions along oneof the pair of substrate faces, such that the responses generated uponexposure of the sensor array to at least one analyte in a fluid flowinclude a spatio-temporal difference between responses generated by eachof the first and the plurality of the second sensors. The sensor arraycan include a plurality of substrates, each substrate forming a platehaving a length, a width, and a depth, such that for each of thesubstrates the length and the width in combination define a pair ofsubstrate faces and the width and the depth in combination define a pairof substrate edges. The substrates can be oriented in the samplingvolume such that the substrate faces extend in a direction parallel to adirection of the fluid flow and the substrate edges are situated normalto the fluid flow. For each of the plurality of substrates, the sensorarray can include one or more first sensors located on one of the pairof substrate edges and one or more second sensors located on at leastone of the pair of substrate faces. At least one of the first sensor orthe second sensors can have a sensor volume substantially optimized toachieve a maximum signal to noise ratio for at least one target analyte.The sensor volume can be substantially optimized as a function of apartition coefficient K of at least one target analyte. Thepredetermined sampling volume can include a headspace proximate to thefirst sensor, the headspace having a headspace volume V_(l). The sensorvolume V_(p) can be substantially optimized based on the functionV_(p)=V_(l)/K. The first sensors can include one, or multiple, vaporsensors for detecting an analyte in a gas. The first sensors can includeone, or multiple, liquid sensors for detecting an analyte in a liquid.

[0015] In general, in another aspect, the invention features methods fordetecting an analyte in a fluid flow. The methods include providing asensor array having a first face and a second face and including one ormore first sensors, exposing the sensor array to a fluid flow includingan analyte under conditions sufficient to create a pressure differentialbetween the first and second faces of the sensor array, measuring aresponse for the first sensors, and detecting the presence of theanalyte in the fluid based on the measured response. The sensor arrayincludes one or more fluid channels extending from the first face to thesecond face. At least one of the first sensors is located at a firstposition in the sensor array in contact with the first face of thesensor array. The first sensors are configured to generate a responseupon exposure of the sensor array to at least one analyte in a fluidflow.

[0016] Particular implementations of the invention can include one ormore of the following features. The sensor array can include a substratehaving a first surface and a second surface. The fluid channels canextend from the first surface to the second surface. The fluid channelscan include a plurality of pores in a microporous substrate material, ora plurality of holes introduced into an impermeable substrate material.The fluid flow system can include a predetermined sampling volume, withthe sensor array located within the sampling volume. The first sensorcan have a sensor volume substantially optimized to cause the firstsensor to generate a response having a maximum signal to noise ratio forat least one target analyte. The sensor volume can be substantiallyoptimized as a function of a partition coefficient K of at least onetarget analyte. The predetermined sampling volume can include aheadspace proximate to the first sensor, the headspace having aheadspace volume V_(l). The sensor volume V_(p) can be substantiallyoptimized based on the function V_(p)=V_(l)/K. The first sensors caninclude one, or multiple, vapor sensors for detecting an analyte in agas. The first sensors can include one, or multiple, liquid sensors fordetecting an analyte in a liquid.

[0017] The sensor array can include at least one second sensor locatedat a second position in the sensor array. The second position can bedifferent from the first position relative to the fluid flow. The firstand second sensors can each generate a response upon exposure of thesensor array to at least one analyte in a fluid flow, such that theresponses generated upon exposure of the sensor array to at least oneanalyte in a fluid flow include a spatio-temporal difference between theresponses for the first and second sensors. Detecting the presence ofthe analyte in the fluid can include resolving a plurality of analytesin the fluid based on the measured response. The sensor array caninclude a plurality of second sensors. Each of the first sensor and aplurality of the second sensors can be located at a different positionin the sensor array relative to the fluid flow. The first and secondsensors can each generate a response upon exposure of the sensor arrayto at least one analyte in a fluid flow, such that the responsesgenerated upon exposure of the sensor array to at least one analyte in afluid flow include a spatio-temporal difference between the responsesfor the first and second sensors.

[0018] The sensor array can include a first substrate forming a platehaving a length, a width, and a depth, such that the length and thewidth in combination define a pair of substrate faces and the width andthe depth in combination define a pair of substrate edges. The firstsubstrate can be oriented in the sampling volume such that the substratefaces extend in a direction parallel to a direction of the fluid flowand the substrate edges are situated normal to the fluid flow. The firstsensors can be located on one of the pair of substrate edges. The sensorarray can include one or more second sensors located on one of the pairof substrate faces. Detecting the presence of the analyte in the fluidincludes resolving a plurality of analytes in the fluid based on themeasured response. The sensor array can include a plurality of secondsensors located at different positions along one of the pair ofsubstrate faces, such that the responses generated upon exposure of thesensor array to at least one analyte in a fluid flow include aspatio-temporal difference between responses generated by each of thefirst and the plurality of the second sensors. The sensor array caninclude a plurality of substrates, each substrate forming a plate havinga length, a width, and a depth, such that for each of the substrates thelength and the width in combination define a pair of substrate faces andthe width and the depth in combination define a pair of substrate edges.The substrates can be oriented in the sampling volume such that thesubstrate faces extend in a direction parallel to a direction of thefluid flow and the substrate edges are situated normal to the fluidflow. For each of the plurality of substrates, the sensor array caninclude one or more first sensors located on one of the pair ofsubstrate edges and one or more second sensors located on at least oneof the pair of substrate faces. At least one of the first sensor or thesecond sensors can have a sensor volume substantially optimized toachieve a maximum signal to noise ratio for at least one target analyte.The sensor volume can be substantially optimized as a function of apartition coefficient K of at least one target analyte. Thepredetermined sampling volume can include a headspace proximate to thefirst sensor, the headspace having a headspace volume V_(l). The sensorvolume V_(p) can be substantially optimized based on the functionV_(p)=V_(l)/K. The first sensors can include one, or multiple, vaporsensors for detecting an analyte in a gas. The first sensors can includeone, or multiple, liquid sensors for detecting an analyte in a liquid.

[0019] In general, in another aspect, the invention features sensorarrays for detecting an analyte in a fluid. The sensor arrays includeone or more substrates and one or more sensors in contact with thesubstrates. Each substrate has a first surface. The sensors areconfigured to generate a response upon exposure of the sensor array toat least one analyte in a fluid. Each sensor has a sensor volume. Thesensor volume for at least one of the sensors is substantially optimizedto cause the first sensor to generate an optimized response uponexposure of the sensor array to at least one target analyte.

[0020] Particular implementations of the invention can include one ormore of the following features. The sensor volume can be substantiallyoptimized as a function of a sampling headspace volume V_(l) and apartition coefficient K of at least one target analyte. The sensorvolume V_(p) can be substantially optimized based on the functionV_(p)=V_(l)/K. The sensors can include two or more optimized sensors.Each of the optimized sensors can be substantially optimized to generatean optimized response upon exposure of the sensor array to a differenttarget analyte. The optimized response can have a substantiallymaximized signal to noise ratio.

[0021] In general, in another aspect, the invention features sensorarrays for detecting an analyte in a fluid flow. The sensor arraysinclude a substrate having a first surface and a second surface, one ormore sensors in contact with the first surface, and one or more fluidchannels extending from the first surface to the second surface. Thesensors are configured to generate a response upon exposure of thesensor array to at least one analyte in a fluid flow.

[0022] Particular implementations of the invention feature one or moreof the following features. The fluid channels can be configured suchthat upon introduction of a fluid flow to the sensor array a pressuredifferential is created between the first and second surfaces of thesubstrate. The substrate can include a microporous material or animpermeable material. The fluid channels can include a plurality ofpores in the substrate, or a plurality of holes introduced into thesubstrate. The sensors can include one, or multiple, vapor sensors fordetecting an analyte in a gas. The sensors can include one, or multiple,liquid sensors for detecting an analyte in a liquid.

[0023] In general, in still another aspect, the invention featuressensor arrays having a first face and a second face for detecting ananalyte in a fluid flow. The sensor arrays include one or moresubstrates, each substrate forming a plate having a length, a width, anda depth, such that the length and the width in combination define a pairof substrate faces and the width and the depth in combination define afirst substrate edge and a second substrate edge; a plurality of sensorsconfigured to generate a response upon exposure of the sensor array toat least one analyte in a fluid flow; and one or more fluid channelsextending along one or more of the substrate faces from the first faceof the array to the second face of the array. The first substrate edgefor each of the substrates is aligned with the first face of the array.The sensors include one or more first sensors sensors and one or moresecond sensors. Each of the first sensors is located along one of thefirst substrate edges. Each of the second sensors is located along oneof the substrate faces.

[0024] Particular implementations can include one or more of thefollowing features. The sensors include a plurality of second sensorslocated at different positions along at least one of the pair ofsubstrate faces, such that the responses generated upon exposure of thesensor array to at least one analyte in a fluid flow include aspatio-temporal difference between responses generated by each of thefirst and the plurality of the second sensors. The sensors include one,or multiple, vapor sensors for detecting an analyte in a gas. Thesensors include one, or multiple, liquid sensors for detecting ananalyte in a liquid.

[0025] In general, in still another aspect, the invention featuresmethods of fabricating a sensor array for detecting an analyte in afluid. The methods include providing a substrate having a surface and asampling headspace proximate to the surface; identifying a samplingheadspace volume V_(l) for at least a portion of the sampling headspace,and a partition coefficient K of at least one target analyte in asensing material; calculating a sensor volume based on the samplingheadspace volume and the partition coefficient; and fabricating a sensoron the surface proximate to the at least a portion of the samplingheadspace, the sensor including an amount of the sensing materialderived from the calculated sensor volume. In particularimplementations, the sensor volume V_(p) can be calculated based on thefunction V_(p)=V_(l)/K.

BRIEF DESCRIPTION OF THE DRAWINGS

[0026]FIG. 1 illustrates one implementation of a system involving alinear sensor array for detecting an analyte in a fluid.

[0027]FIG. 2 illustrates a two-dimensional implementation of a sensorarray for detecting an analyte in a fluid.

[0028]FIG. 3 illustrates one implementation of a perforatedtwo-dimensional sensor array.

[0029]FIGS. 4A and 4B illustrate a flow-through sensor systemincorporating the perforated array such as is shown in FIG. 3.

[0030]FIGS. 5A and 5B illustrate an implementation of a system fordetecting an analyte in a fluid involving a stacked sensor array.

[0031]FIG. 6 is a diagram illustrating the equilibration between afinite volume of sampled analyte and a finite volume of sorption-basedvapor detection film in a sensor array according to the invention.

[0032]FIG. 7 illustrates a plot of the power spectral density of noiseversus frequency for seven polymer-carbon black composite detector filmsaccording to the invention.

[0033]FIGS. 8A and 8B illustrate plots of spectral density of noisetimes frequency and the square of noise values as a function of volumefor two polymer-carbon black composite detector films.

[0034]FIGS. 9A and 9B illustrate a plot of differential frequencychanges of quartz crystal microbalances coated with two polymer filmsduring exposure to hexane and methanol.

[0035]FIG. 10 is a table showing responses, noise, and S/N for two typesof polymer-carbon black composite detectors in the configuration of FIG.5A.

[0036]FIG. 11 illustrates a plot of normalized relative differentialresistance responses of polymer-carbon black composite detectors exposedto a high vapor pressure analyte (hexane), a moderately low vaporpressure analyte (dodecane) and a low vapor pressure analyte (tridecane)at a constant activity and volumetric flow rate.

[0037]FIGS. 12A and 12B illustrate plots of normalized relativedifferential resistance responses for two different polymer-carbon blackcomposite detectors to hexane and dodecane at a constant activity inair.

[0038]FIG. 13 illustrates a plot of resistance response as a function oftime for a polymer-carbon black composite detector exposed to bothhexane and a mixture of hexane and dodecane.

[0039]FIGS. 14A and 14B illustrate the relative differential resistanceresponses to hexane and dodecane after 40 seconds and 200 seconds ofpolymer-carbon black composite detectors located on the edge and faceportions of a stacked sensor array as shown in FIG. 5A.

[0040]FIG. 15 illustrates one implementation of the stacked sensor arrayof FIG. 5A, involving 18 different detectors constructed from ninedifferent sensor materials.

[0041]FIG. 16 illustrates the average differential resistance responsecomputed as the baseline normalized differential resistance change ofthe detectors in the stacked sensor array of FIG. 15 after exposure todinitrotoluene in the presence of two potentially interfering compounds.

[0042]FIG. 17 illustrates the normalized array fingerprint patterns ofpure dinitrotoluene and DNT in the presence of large concentrations ofacetone or water for the sensor array of FIG. 15.

DETAILED DESCRIPTION OF THE INVENTION

[0043]FIGS. 1A, 1B and 1C illustrate one example of a system 100 fordetecting an analyte in a fluid. System 100 includes a sensor array 110,including a plurality of sensors 120 arranged on a substrate 125 along afluid channel 130. In some implementations, sensor array 110 may beconfigured to include one or more fluid channels in addition to fluidchannel 130, such as fluid channel 140 including additional sensorsarranged along the same or a different substrate. A fluid to beanalyzed, which may be in gaseous or liquid form, is introduced tosensor array 110 through fluid inlet 160, for example from fluidreservoir 170. Response signals from the sensors 120 in sensor array 110resulting from exposure of the fluid to the sensor array are receivedand processed in detector 180, which may include, for example,signal-processing electronics, a general-purpose programmable digitalcomputer system of conventional construction, or the like.

[0044] Sensors 120 can include sensors of any of a variety of knowntypes, including, for example, surface acoustic wave sensors, quartzcrystal resonators, metal oxide sensors, dye-coated fiber optic sensors,dye-impregnated bead arrays, micromachined cantilever arrays,vapochromic metalloporphyrins, composites having regions of conductingmaterial and regions of insulating organic material, composites havingregions of conducting material and regions of conducting orsemiconducting organic material, chemically-sensitive resistor orcapacitor films, metal-oxide-semiconductor field effect transistors,bulk organic conducting polymeric sensors, and other known sensor types.Techniques for constructing arrays of such sensors are known, asdisclosed in Harsanyi, G., Polymer Films in Sensor Applications(Technomic Publishing Co., Basel, Switzerland, 1995), and U.S. Pat. Nos.6,017,440, 6,013,229 and 5,911,872 and co-pending U.S. patentapplication Ser. No. 09/409,644, filed Oct. 1, 1999, which areincorporated by reference herein. Techniques for fabricating particularsensor types are disclosed in Ballantine, et al., Anal. Chem. 1986, 58,3058; Grate, et al., Sens. Actuators B 1991, 3, 85; Grate, et al., Anal.Chem. 1993, 65, 1868; Nakamoto, et al., Sens. Actuators B 1993, 10, 85(surface acoustic wave (SAW) devices), Gardner, et al., Sens. ActuatorsB 1991, 4, 117; Gardner, et al., Sens. Actuators B 1992, 6, 71;Corcoran, et al., Sens. Actuators B 1993, 15, 32 (tin oxide sensors),Shurmer, et al., Sens. Actuators B 1991, 4, 29; Pearce, et al., Analyst1993, 118, 371 (conducting organic polymers), Freund, et al., Proc.Natl. Acad. Sci. 1995, 92, 2652 (materials having regions of conductorsand regions of insulating organic material), White, et al., Anal. Chem.1996, 68, 2191 (dye-impregnated polymer films on fiber optic sensors),Butler, et al., Electrochem. Soc. 1990, 137, 1325; Hughes, et al.,Biochem. and Biotechnol. 1993, 41, 77 (polymer-coated micromirrors),Slater, et al., Analyst 1994, 119, 191; Slater, et al., Analyst 1991,116, 1125 (quartz crystal microbalances (QCMs)), Keyvani, et al., Sens.Actuators B 1991, 5, 199 (electrochemical gas sensors), Zubkans, et al.,Thin Solid Films 1995, 268, 140 (chemically sensitive field-effecttransistors) and Lonergan, et al., Chem. Mater. 1996, 8, 2298 carbonblack-polymer composite chemiresistors). Additional sensor arrayfabrication techniques are disclosed in Albert, K. J., et al., Chem.Rev., 2000, 100, 2595-2626 and the references cited therein.

[0045] In one implementation, sensor array 110 incorporates multiplesensing modalities, for example comprising a spatial arrangement ofcross-reactive sensors 120 selected from known sensor types, such asthose listed above, such that a given analyte elicits a response frommultiple sensors in the array and each sensor responds to many analytes.Preferably, the sensors in the array 110 are broadly cross-reactive,meaning each sensor in the array responds to multiple analytes, and, inturn, each analyte elicits a response from multiple sensors.

[0046] Sensor arrays allow expanded utility because the signal for animperfect “key” in one channel can be recognized through informationgathered on another, chemically or physically dissimilar channel in thearray. A distinct pattern of responses produced over the collection ofsensors in the array can provide a fingerprint that allowsclassification and identification of the analyte, whereas suchinformation would not have been obtainable by relying on the signalsarising solely from a single sensor or sensing material. By developingan empirical catalogue of information on chemically diversesensors—made, for example, with varying ratios of semiconducting,conducting, and insulating components and by differing fabricationroutes—sensors can be chosen that are appropriate for the analytesexpected in a particular application, their concentrations, and thedesired response times. Further optimization can then be performed in aniterative fashion as feedback on the performance of an array underparticular conditions becomes available.

[0047] In some implementations, the sensor arrays of system 100incorporate spatiotemporal response information that is used by detector180 to aid in analyte detection and identification. The incorporation ofdata derived from spatio-temporal properties of a sensor array canimpart useful information on analyte detection and identificationrelative to arrays where no spatiotemporal information is availablebecause all sensors are nominally in identical positions with respect tothe fluid flow characteristics and are exposed to the analyte atnominally identical times during the fluid sampling experiment.Electronics can be implemented in detector 180 to record a time delaybetween sensor responses and to use this information to characterize theanalyte of interest in the fluid. This mode can also be advantageousbecause it can allow automatic nulling of any sensor drift,environmental variations (such as temperature, humidity, etc.) and thelike. Also, a complex analyte mixture can be better resolved into itscomponents based on the spatiotemporal characteristics of the arrayresponse relative only to the differences in fingerprints on the varioussensors types in the array. Additionally, the method can be used inconjunction with differential types of measurements to selectivelydetect only certain classes or types of analytes, because the detectioncan be gated to only focus on signals that exhibit a desired correlationtime between their responses on the sensors that are in differentexposure times relative to the sensor response on the first sensor thatdetects an analyte.

[0048] Thus, for example, sensor arrays 110 can be configured such thatlow vapor pressure analytes in the gas phase will have a high affinitytowards the sensors and will sorb strongly to them. This strong sorptionproduces a strong response at the first downstream sensor that theanalyte encounters, a weaker response at the second downstream sensor,and a still weaker response at other downstream sensors. Differentanalytes will produce a detectable and useful time delay between theresponse of the first sensor and the response of the other downstreamsensors. As a result, detector 180 can use the differences in responsetime and amplitude to detect and characterize analytes in a carrierfluid, analogous to the use of gas chromatography retention times, whichare well known in the gas chromatography literature and art.

[0049] Spatio-temporal information can be obtained from an array of twoor more sensors by varying the sensors' exposure to the fluid containingthe analyte across the array (e.g., by generating a spatial and/ortemporal gradient across the array), thereby allowing responses to bemeasured simultaneously at various different exposure levels and forvarious different sensor compositions. For example, an array can beconstructed in two dimensions with sensors arranged at the vertices of agrid or matrix. Such arrays can be configured to vary the composition ofthe sensors in the horizontal direction across the array, such thatsensor composition in the vertical direction across the array remainsconstant. One may then create a spatio-temporal gradient in the verticaldirection across the array—for example, by introducing the fluid fromthe top of the array and providing for fluid flow vertically down thearray, thereby allowing the simultaneous analysis of chemical analytesat different sensor compositions and different exposure levels.Similarly, in an array 110 including a plurality of different sensors120 (i.e., an array in which each sensor is of a different type orcomposition), spatio-temporal variation can be introduced bysystematically varying the flow rate at which the analyte-containingfluid is exposed to the sensors in the array. Again, in thisimplementation, measuring the response of each of the sensors 120 at avariety of different flow rates allows the simultaneous analysis ofanalytes at different sensor compositions and different exposure levels.

[0050] Thus, in one implementation, the sensors defining each fluidchannel are nominally identical—that is, the sensors within a givenfluid channel are identical—while the array incorporates a predeterminedinter-sensor variation in the chemistry, structure or composition of thesensors between different fluid channels. The variation can bequantitative and/or qualitative. For example, different channels can beconstructed to incorporate sensors of different types, such asincorporating a plurality of nominally identical metal oxide gas sensorsin a first fluid channel, a plurality of conducting polymer sensors inan adjacent fluid channel, and so on across the array. Alternatively,compositional variation can be introduced by varying the concentrationof a conductive or semiconductive organic material in a composite sensoracross fluid channels. In still another variation, a variety ofdifferent organic materials may be used in sensors in differentchannels. Similar patterns of introducing compositional variation intosensor arrays will be readily apparent to those skilled in the art.

[0051] Although FIG. 1A depicts the fluid channels as linear channelsextending in just one direction, sensor arrays can be configured toprovide similar fluid channels having different geometries—for example,arrays with sensors arranged in two or more directions relative to thefluid flow, such as a circular array having a radial arrangement ofsensors around a fluid introduction point. FIG. 2 illustrates a simplysensor array of this type—an array 200 of eight sensors 210. A stream220 of fluid containing an analyte or analytes of interest is directedat surface 230, such that the stream contacts surface 230 at point 240,and then flows radially in both directions across the array.

[0052] While sensor array 110 has been described as incorporating one ormore fluid channels each comprising a plurality of nominally identicalsensors, those skilled in the art will recognize that the techniquesdescribed herein can be used to generate useful spafio-temporalinformation from arrays including a plurality of sensors all ofdifferent chemistry, structure or composition, with the fluid path beingdefined by the introduction of the fluid onto the array. In thisimplementation, spatio-temporal response data can be generated byintroducing the fluid onto the array at varying flow rates, for example,by using a flow controller of known construction to systematically varythe rate at which the fluid is introduced over time. Alternatively, flowrate variation can be introduced by simply exposing the array to anaturally varying fluid flow, such as a flow of air.

[0053] In some implementations, system 100 provides that an analyte(e.g., a gas analyte) can be directed through or to substrate 125 byincluding gaps or pores into the substrate or by using a substrate thatitself is porous and highly permeable to the analyte of interest.Application of a pressure differential between the top and bottom of thesubstrate allows the gas to be effectively sampled by the detectors(e.g., a sensor film deposited on substrate 125), enhancing thedetection sensitivity of the entire sensor device and system.

[0054] In one implementation, illustrated in FIG. 3, sensors 300 arearranged on a surface 310 of porous substrate 320 such that a fluidcontaining the analyte or analytes of interest strikes surface 310,interacts with sensors 300, and flows through pores 330. Sensors 300 canbe fabricated as a sensor film deposited on top of substrate 320. Asillustrated in FIG. 4A, a pressure differential can be establishedbetween the two sides 410 and 420 of a perforated or porous substrate400 in order to direct the analyte to flow through the sensor film,optimizing analyte sorption and detection performance, as opposed tomerely flowing nearby or parallel to the surface of a solid substrate430. One example of a flow-through apparatus incorporating such aperforated substrate is illustrated in FIG. 4B. A variety of differentsubstrates, with a variety of different porosities can be used.

[0055] Substrate 320 can be fabricated from a material that is nothighly permeable by the analyte gas of concern, such as printed circuitboard, ceramic, or a silicon wafer. In this embodiment, pores 330 cantake the form of a series of holes introduced into the substrate atwell-defined positions and spacings. Hole density, hole diameter and/orsensor size can be optimized for a given analyte flow rate, analytegas/solid partition coefficient, and analyte permeability into thesensor film, in order to allow the maximum amount of analyte to becaptured by the sensor film during its flow by the sensor and sensorsubstrate.

[0056] For analytes having low vapor pressure (and high partitioncoefficients), larger detector areas will produce a dilution of theavailable analyte into larger detector volumes, thereby producing lessresistance change in such detector films. Because the sensor responsescales linearly with the concentration of sorbed analyte, whereas thenoise scales as the square root of the detector film area (for constantfilm thickness), this favors smaller detector areas.

[0057] Thus, for low vapor pressure analytes, a preferred a flow-throughdetector configuration incorporates roughly 2-25% open area (98%-75%solidity, with the exact value depending on the analyte's partitioncoefficient into the polymer film) for analyte detection. Simulations ofdetectors having 1% open area suggest that the capture effectiveness ofthe perforated plate arrangement scales with the flow Reynolds number.However, the capture effectiveness can be bounded from below by 50% forReynolds numbers up to 100, which can correspond to the limiting case ofa detector with one or two holes and an open area of 1-2%. It may besufficient to have enough holes to ensure even flow into the detector.Significant improvements over this design (up to ˜90% analyte capture)can be expected when the Reynolds number is on the order of 1 (very manysmall holes, e.g., approximately 1 μm in diameter spaced at, e.g., 12 μmintervals). Micro-machining methods may be required to satisfy thesedimensions.

[0058] Alternatively, substrate 320 can be fabricated from a materialthat is porous to analyte flow. The porosity can be introduced throughphysical or chemical processes. Two such examples are Anopore aluminamembranes and Nucleopore polymer membranes. As described above, optimumpore structure and pore distribution can be computed for certainspecific conditions of analyte flow velocity, gas/polymer sorptioncoefficient, and other sensor and sensor parameters.

[0059] In a preferred implementation, the porous substrate is amicroporous, branched-pore Anopore membrane having 200 nm diameter poresextending from one face through most of the membrane thickness,branching to 20 nm diameter pores in a narrow layer (e.g., 500 nm in a60 micron membrane) at the opposite face. Sensors are deposited as thinfilms on this face (on top of conductive contacts deposited on thesurface) using techniques such as those described below. Thebranched-pore membrane structure ensures that the detector face presentspores of a sufficiently small diameter to limit seepage of the sensormedia into the membrane (e.g., excluding carbon black particles in apolymer-carbon black composite film as described below having particlesizes ranging from about 20 nm to about 50 nm), while also providing fora high fluid flux to the sensor film.

[0060] In another implementation, illustrated in FIGS. 5A and 5B, theholes/pores can be replaced by their one-dimensional analog—linear ornon-linear channels or gaps 500 in spacing through plates 510 thatcontain sensors on their edges 520. The performance of this type ofsystem can also be computed using well-known equations for specificsensor/substrate conditions. In some instances, this type of structurecan be easier to manufacture than one with holes in the substrate. Inaddition, this type of structure offers the opportunity to introduceadditional sensors 530 on the faces 540 of the stacked substrates,offering an opportunity to make measurements on sensor films placed bothon the edges of the substrates as well as at various positions and invarious geometries on the faces of the substrates. Measurement of theresponse at various positions on the substrate in this type of geometrypermits the parallel analysis of vapors that possess different optimalsorption and/or detection regions on the sensor material in the presenceof the flow onto and around the stacked substrates.

[0061] The incorporation of different form factors of a given detectorfilm in conjunction with specific types of analyte flow paths canprovide very different detection performance for different types ofanalyte vapors. Accordingly, as will be described in more detail below,the use of an array of detectors that are nominally identicalchemically, but which have different form factors relative to theanalyte flow path, can provide useful information on the composition andidentity of an analyte vapor. In addition, the arrangement of FIGS. 5Aand 5B offers a simple means to differentiate between target analytesand background contaminants, even where the contaminants are present atsignificantly higher concentration than the target analyte, as will bedescribed in more detail below.

[0062] In some implementations, the form factor of the sensors in thearray can be manipulated to optimize the signal to noise output of thesystem, yielding one or more sensors having optimal, or near-optimal,sensor volumes for one or more target analytes. At open circuit,resistors exhibit voltage fluctuations—known as Johnson noise—whosepower spectrum is constant as the frequency is varied. The root meansquared (rms) noise voltage density of the Johnson noise, V_(JN), isrelated to the resistance, R, of a resistive detector as follows:

V _(JN)=(4kTRB)^(½)  (1)

[0063] where k is Boltzmann's constant, T is the temperature in degreesK, and B is the bandwidth (Wilmshurst, T. H., Signal Recovery from Noisein Electronic Instrumentation; Adam Hilger Ltd: Boston, 1985). ThisJohnson noise is the fundamental lower limit on the noise of any deviceof resistance R, and its magnitude is independent of the volume or ofother fabrication-dependent properties of the resistor. However, whencurrent flows through most types of resistive materials, a voltagefluctuation is observed with a power spectral density that displays aninverse dependence on frequency. This additional noise, which istypically of the form 1/f^(γ) where γ=1±0.1, is designated 1/f noise(Larry, et al., IEEE Trans. Comp. Hybrids, Manufact. Technol. 1980,CHMT-3, 211-225; Weissman, M. B. Rev. Mod. Phys. 1988, 60, 537-571).

[0064] Even for a series of resistors that are fabricated by anidentical process, the magnitude of the 1/f noise depends on the volume,V, of the resistor. When the correlation length of the resistiveparticle network is small compared to the physical length scale ofinterest, the 1/f noise of a resistance-based detector is expected to beproportional to V^(−½) (Dziedzic, et al., J. Phys. D-Appl. Phys. 1998,31, 2091-2097). For a given film thickness, this implies that the totalnoise of a resistive detector scales as A^(−½), where A is the totalarea of the detector film between the electrical contact leads. Thisdependence requires that the magnitude of the 1/f noise, in thefrequency window of the measurement, is much greater than the magnitudeof the Johnson noise, so that the total noise is dominated by the 1/fcontribution.

[0065] As a consequence of Ohm's law, the power spectral density,S_(n)(V), of the 1/f resistance noise scales with the square of the biasvoltage, V_(b), applied to the resistor. The quantity of fundamentalinterest in characterizing the noise of a resistive detector element isthus:

S _(n) =S _(n)(V _(b))/V _(b) ²  (2)

[0066] where S_(n) is the relative noise power spectral density andV_(b) is the biasing voltage (Dziedzic, et al., J. Phys. D-Appl. Phys.1998, 31, 2091-2097; Scofield, et al., Phys. Rev. B 1981, 24,7450-7453). In contrast to the Johnson noise, the level of the 1/f noisein carbon black polymer composite resistors varies with many factors,including the structure of the carbon black, its volume fraction in thecomposite, the type of insulator, the resistivity of the composite, andthe method of resistor preparation (Dziedzic, et al., J. Phys. D-Appl.Phys. 1998, 31, 2091-2097; Fu, et al., IEEE Trans. Comp. HybridsManufact. Technol. 1981, 4, 283-288).

[0067] The dependence of the signal produced by sorption of an analyteon the volume of the detector film can be determined as follows.Consider introducing a fixed quantity of an analyte into a samplechamber of total volume V_(l) to produce an initial analyteconcentration C_(v) ^(i) in the vapor phase, as illustrated in FIG. 6.The analyte can either be introduced as a pulse of concentrated analyteinto the volume V_(l) or by introducing a sampled volume of analyte inconjunction with a dead volume of carrier gas in the sampling path suchthat initially after the sampling process has been completed, an analyteconcentration C_(v) ^(i) is present in a total headspace volume V_(l) .Assuming that no analyte is present initially in either the backgroundgas or the polymer, the total number of moles of analyte available forsorption into the polymer is therefore n_(T)=C_(v) ^(i) V_(l). Sorptionof the analyte into a polymer of volume V_(p) will proceed with apolymer/gas partition coefficient, K=C_(p)/C_(v) ^(eq), where C_(p) isthe concentration of analyte in the polymer phase, C_(v) ^(eq) is theconcentration of the analyte in the vapor phase, and both concentrationsrefer to the situation after equilibrium has been reached.

[0068] For typical detector film thicknesses of 0.2-1.0 μm, and fortypical headspace thicknesses of greater than 0.1 cm, even 100%increases in film thickness due to sorption-induced film swelling willproduce a negligible change in the headspace volume. Assuming that thechange in volume of the polymer phase due to analyte sorption, ΔV_(p),is generally small compared to the value of the initial headspace volumeV_(l) implies that V_(l) also equals the headspace volume afterequilibrium has been reached. Under these conditions, conservation ofmass of analyte implies that:

n _(T) =V _(l) C _(v) ^(i) =V _(p) C _(p) +V _(l) C _(v) ^(eq)  (3)

[0069] Hence

n _(T) =V _(p) C _(p) +V _(l) C _(p) /K  (4)

[0070] or

C _(p) n _(T)/(V _(p) +V _(l) /K)  (5)

[0071] It can be further assumed (Albert, et al., Chem. Rev. 2000, 100,2595-2626) that the signal, S, obtained due to sorption of analyte intothe polymer is linearly related to the sorbed analyte concentrationthrough a sensitivity factor, X₁, for each analyte/polymer combination:

S=X ₁ C _(p)  (6)

[0072] In the limit where the 1/f noise dominates the total noise of achemically sensitive resistor, this measurement noise, N, scales asV^(−½) (vide supra). It follows that:

N=X ₂ V _(p) ^(−½)  (7)

[0073] where X₂ is a constant that is independent of the film volume.

[0074] The signal/noise is therefore:

S/N=X ₁ C _(p) /X ₂ V _(p) ^(−½)  (8)

[0075] Substituting for C_(p) from Equation 5, above, produces:

S/N=(X ₁ /X ₂)n _(T) [V _(p) ^(½)+(V _(l) /K)V _(p) ^(−½]) ⁻¹  (9)

[0076] Multiplying both the numerator and denominator of the right handside of Equation 9 by (K/V_(l))^(½) yields:

S/N=(X ₁ /X ₂)n _(T) (K/V _(l))^(½)[(V _(l) /K)^(−½)+(V _(l) /K)^(½) V_(p) ^(−½)]⁻¹   (10)

[0077] With the substitution x=V_(p)K/V_(l), Equation 10 becomes:

S/N=(X ₁ /X ₂)n _(T) (K/V _(l))^(½) [x ^(½) +x ^(−½)]⁻¹  (11)

[0078] This function is maximized when x=1, i.e., when K V_(p)/V_(l)=1,which implies that:

V _(p) =V _(l) /K  (12)

[0079] at maximal S/N ratio.

[0080] When V_(p)=V_(l)/K, Equations 3 and 4 yield C_(v) ^(eq) V_(l)=(½)n_(T) and C_(p) V_(p)=(½) n_(T). In other words, for a finite quantityof sampled analyte, the maximal S/N ratio is obtained when the detectorvolume equals the headspace volume V_(l) divided by the polymer/gaspartition coefficient. This produces a situation in which equal numbersof moles of analyte are present in the polymer and vapor phases afterequilibrium has been attained.

[0081] In practice, the film thickness of the detector is typically assmall as possible to minimize the time constant for sorbtion/desorbtionof analyte. Hence, at constant, minimized film thickness, Equations 9and 12 imply that there is an optimum detector film area for a givenheadspace volume and a given initial headspace analyte concentration.Smaller detector areas than this optimum value fail to exhibit optimallylow noise, while larger detector areas result in the sorption of thefixed number of moles of analyte into too large of a polymer volume andtherefore produce a reduced magnitude of signal after equilibrium hasbeen reached. Another consequence of this analysis is that the differentresponse properties of a set of detectors having a common polymersorbent layer, but having different form factors, can provideinformation on the value of K, if V_(l) is known and/or is held constantduring the experiment. The validity of these predictions has beenconfirmed for sorption-based detectors fabricated using carbonblack-filled chemiresistors as exemplary systems, as will be describedin more detail below.

[0082] In implementations employing sensors comprised of carbonblack-polymer composite chemiresistors, sensor performance, measured asthe baseline normalized differential resistance change (ΔR/R_(b)) islinearly dependent on analyte concentration over a range ofanalyte/detector combinations and analyte concentrations (Severin, etal., Anal. Chem. 2000, 72, 658-668). Detection limits for such sensorscan be estimated based on noise measurements, in conjunction with thedependence of ΔR/R_(b) on the partial pressure of the analyte (Doleman,et al., Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 5442-5447), and theanalyte/polymer sensitivity factors that can be deduced from such plots.Two limiting cases are illustrative: a) high vapor pressure analytes,which have relatively small partition coefficients for sorption into thecarbon black composite detectors, and b) low vapor pressure analytes,which generally sorb strongly and exhibit very large polymer/gaspartition coefficients into the polymers of concern.

[0083] When the polymer/gas partition coefficient is relatively small,sufficient analyte will, in general, be present in the sampled volume toproduce the equilibrium volume swelling of the entire available detectorarea. In this situation, too little detector volume is generally presentto satisfy the optimum detector volume as given by Equation 12. Atconstant film thickness, the steady-state ΔR/R_(b) value of a givencarbon black/polymer composite is directly related to the swellingchange of the film. Thus, a given analyte concentration should producethe same steady-state ΔR/R_(b) signal in the film regardless of the areaof such a detector.

[0084] Under these conditions, the scaling of the S/N (in a givenmeasurement bandwidth) with detector area is determined by thedependence of the noise on detector area. As discussed above, thebackground noise of the carbon black composite chemiresistors at lowmeasurement frequencies scales as A^(−½). The S/N, and thus thedetection limits of a particular carbon black polymer composite detectortowards a given analyte, therefore scale as A^(½). The use of a detectorfilm having the largest practical volume possible (up to the limit ofoptimum volume indicated by Equation 12, or the volume at which the 1/fnoise, for the measurement bandwidth, falls below the Johnson noise andthe total noise no longer exhibits a dependence on volume) is thus theoptimum detector design under such conditions.

[0085] S/N values and deduced limits of detection for representativecarbon black/polymer composite detectors with various vapor analytes,for 1 cm² of detector area are illustrated in Table 1, in which limitsof detection are calculated from the slopes of ΔR/R_(b) vs. P/P^(o) at294 K as described in Severin, et al., Anal. Chem. 2000, 72, 658-668,using 3σ noise values for 1 cm² of the same film type at averageexperimental film thickness values of 230 nm for PEVA and 80 nm for PCL.TABLE 1 Limits of Detection for Carbon Black Polymer Composite Detectorsand Polymer Film SAW Detectors LOD (μg/L) polymer benzene cyclohexanonehexane nonane Carbon Black Composite PEVA 1.8 × 10¹ 1.5 4.0 × 10¹ 1.3PCL 5.2 × 10² 4.5 × 10¹ 1.3 × 10³ 4.8 × 10¹ SAWpoly[bis(cyanoallyl)siloxane] 4.0 × 10² 1.5 × 10¹ 5.3 × 10³ 5.7 × 10²poly(methylphenylsiloxane) 3.0 × 10² 1.4 × 10¹ 1.5 × 10³ 1.1 × 10²poly(phenyl ether) 2.2 × 10² 1.3 × 10¹ 9.9 × 10² 7.9 × 10¹poly(isobutylene) 2.6 × 10² 3.2 × 10¹ 3.5 × 10² 1.9 × 10¹

[0086] Table 1 also reports representative values taken from theliterature for selected polymer-coated SAW vapor detectors for 158-MHzSAW oscillators at 298 K (Patrash, et al., Anal. Chem. 1993, 65,2055-2066). For the given area, the detection limits are comparable forboth types of signal transduction, although the carbon black compositesexhibit somewhat higher sensitivity than the SAW devices for theanalyte/polymer combinations chosen for comparison. Table 1 reports onlylimits of detection as opposed to limits of classification; the formerquantity depends only on the properties of the analyte/detectorcombination, while the latter quantity also depends on the test set ofanalytes presented to the array as well as on the algorithms used toperform the classification. As reported by Zellers, et al., Anal. Chem.1998, 70, 4191-4201, in at least one instance, the limit ofclassification of an analyte has been shown to be within a factor ofthree of the limit of detection of that same analyte, indicating thatthe limit of classification is likely to be on the same order ofmagnitude as the limit of detection, at least for some tasks.

[0087] In the limit where the analyte exhibits a very strong sorptioninto the polymer film of the carbon black composite detector, adifferent S/N optimization methodology applies. As given by Equation 5,the sorption process under such conditions will be limited by the amountof analyte in the sampled volume. The ΔR/R_(b) signal of the detector isproportional to the swelling change of the detector film (Severin, etal., Anal. Chem. 2000, 72, 2008-2015), so increasing the detector areawill reduce the signal (by diluting the fixed amount of sorbed analyteinto a correspondingly larger volume of polymer). As long as theswelling is linearly dependent on the concentration of analyte sorbedinto the polymer, this dilution will produce a linear decrease in theΔR/R_(b) signal with increased detector volume. Because the noise scalesas A^(−½) (at constant film thickness), the S/N under such conditionsscales as A^(−½) and small detector areas are favored. The design goalunder such conditions is to insure that the most analyte is sorbed intothe least area of detector film, and signals should only be acquiredfrom the limited, highly analyte-swollen, portion of the detector. Thisprinciple is exemplified in the detector arrangement of FIGS. 5A and 5B.

[0088] This relationship also has implications for sample chamber designof vapor detector arrays. Assuming, for example, that the analyteheadspace is comprised of a vertical column equal in area to the area ofthe detector film, and that the detector film thickness is 1.0×10⁻⁴ cm,for analytes having a partition coefficient K=1.0×10², the sorbedanalyte will come to equilibrium with the vapor phase analyte that iscontained in a headspace thickness of 1.0×10⁻². In this instance,increasing the thickness of the headspace provides more analyte than isneeded to attain the optimal S/N ratio for the detector response andrequires introduction of more sample into the headspace chamber.Alternatively, under these circumstances larger detector areas can beused advantageously to obtain improved S/N ratios from the increasednumber of analyte molecules available in a thicker headspace chamber. Incontrast, for K=1.0×10⁷, a 1.0×10⁻⁴ cm thick detector film will sorbessentially all of the analyte from a 1000 cm thick headspace. A 2.6 cm²area of such a detector film could sorb essentially all of the analytein a 3.0×10⁻² cm thick headspace that is supplied at a continuousvolumetric flow rate of 10 cm³ min⁻¹ for a period of 260 min. Forshorter analyte injection times (at constant analyte flow rate), smallerdetector areas are optimal because otherwise the fixed amount of analyteis distributed into too large a detector area, thereby diminishing themagnitude of the signal and deleteriously affecting the S/N ratio of thedetector.

[0089] Given the reported relationships between the mass loading ofanalyte and the ΔR/R_(b) values for carbon black composite vapordetectors (Severin, et al., Anal. Chem. 2000, 72, 2008-2015), inconjunction with the background noise levels reported herein, detectionlimits can be evaluated in the high sorption/low analyte vapor pressureregime. At a noise level of ≈10 ppm, and with a ΔR/R_(b)=0.10 producedat a mass loading of 5.0 μg of analyte sorbed into 1 cm² of polymer, thecomputed 3σ detection limit of a PCL-carbon black composite is 1.5 ngcm⁻². This value can only be reached in practice if an efficientsampling and delivery system is available, such that the full amount ofthe sampled analyte can be delivered effectively to the 1 cm² area ofthe detector film. Of note is that the detection limit scales inverselywith the film area and linearly with the efficiency of deliveringanalyte to the sampled film area.

[0090] In the intermediate sorption/partition coefficient regime, anoptimum detector volume exists for which the S/N, and therefore thedetection limit performance, of a particular analyte/polymer combinationis maximized. This detector volume, and consequently the optimum filmarea, depends only on the analyte/polymer partition coefficient and thesampled analyte volume, and can be calculated from Equation 12. The S/Ncan therefore be optimized for different vapor pressure analytes throughcontrol over the form factor of the detector film. Those skilled in theart will recognize that the use of these techniques to prepare sensors,sensor arrays, and sampling systems having substantially optimal, ornear-optimal, form factors does not depart from the invention.

[0091] The dependence of optimum detector area on the analyte/polymerpartition coefficient can also be used advantageously in theclassification of analytes and analyte mixtures. In such a system,analytes with a high polymer/gas partition coefficient (generallyanalytes with low vapor pressures) would be sorbed into the smallestdetector area possible, producing the largest signal and therefore thelargest S/N ratio for that particular analyte/polymer/samplercombination. Higher vapor pressure analytes are, in turn, detected withhigher S/N performance at detectors having larger film areas. Thus, anarray of contacts spaced exponentially along a polymer film can be usedadvantageously to gain information on the sorption coefficients ofanalytes into polymers, and therefore can provide additionalclassification information on analytes and analyte mixtures relativeonly to equilibrium ΔR/R_(b) values on a detector film having a single,fixed form factor for all analytes. Additional information is availableif the analyte flow rate is also varied over the detector array.Variation in the geometric form factor of detectors can also providepractical advantages in the implementation of instruments based onarrays of vapor detectors. Although information similar to that producedby a collection of spatiotemporally arrayed detectors could in principlebe obtained from an analysis of the time response of a collection ofdetectors that are equivalent both geometrically and with respect to thepoint of analyte injection, the spatiotemporal implementation discussedabove has the advantage that analytes are detected on films that havenearly optimal S/N for the analyte of interest. In addition,electronically referencing the response of a face detector to that of anedge detector, for example, allows nulling of the response to a highvapor pressure analyte and subsequent amplification of only thosesignals arising from low vapor pressure analytes. Finally, deliberatevariation in the analyte flow rate can be used to encode the analytesignal at higher frequencies, and use of a lock-in amplifier centered atthis higher frequency (where the magnitude of the 1/f noise is lowerthan at dc) would enhance the S/N of these detectors.

[0092] The sensors and sensor arrays disclosed herein can act as“electronic noses” to offer ease of use, speed, and identification ofanalytes and/or analyte regions all in a portable, relativelyinexpensive implementation. Thus, a wide variety of analytes and fluidsmay be analyzed by the disclosed sensors, arrays and noses so long asthe subject analyte is capable generating a differential response acrossa plurality of sensors of the array. Analyte applications include broadranges of chemical classes such as organics including, for example,alkanes, alkenes, alkynes, dienes, alicyclic hydrocarbons, arenes,alcohols, ethers, ketones, aldehydes, carbonyls, carbanions, biogenicamines, thiols, polynuclear aromatics and derivatives of such organics,e.g., halide derivatives, etc., biomolecules such as sugars, isoprenesand isoprenoids, fatty acids and derivatives, etc. Accordingly,commercial applications of the sensors, arrays and noses includeenvironmental toxicology and remediation, biomedicine, materials qualitycontrol, food and agricultural products monitoring, anaestheticdetection, automobile oil or radiator fluid monitoring, breath alcoholanalyzers, hazardous spill identification, explosives detection,fugitive emission identification, medical diagnostics, fish freshness,detection and classification of bacteria and microorganisms both invitro and in vivo for biomedical uses and medical diagnostic uses,monitoring heavy industrial manufacturing, ambient air monitoring,worker protection, emissions control, product quality testing, leakdetection and identification, oil/gas petrochemical applications,combustible gas detection, H₂S monitoring, hazardous leak detection andidentification, emergency response and law enforcement applications,illegal substance detection and identification, arson investigation,enclosed space surveying, utility and power applications, emissionsmonitoring, transformer fault detection, food/beverage/agricultureapplications, freshness detection, fruit ripening control, fermentationprocess monitoring and control applications, flavor composition andidentification, product quality and identification, refrigerant andfumigant detection, cosmetic/perfume/fragrance formulation, productquality testing, personal identification,chemical/plastics/pharmaceutical applications, leak detection, solventrecovery effectiveness, perimeter monitoring, product quality testing,hazardous waste site applications, fugitive emission detection andidentification, leak detection and identification, perimeter monitoring,transportation, hazardous spill monitoring, refueling operations,shipping container inspection, diesel/gasoline/aviation fuelidentification, building/residential natural gas detection, formaldehydedetection, smoke detection, fire detection, automatic ventilationcontrol applications (cooking, smoking, etc.), air intake monitoring,hospital/medical anesthesia & sterilization gas detection, infectiousdisease detection and breath applications, body fluids analysis,pharmaceutical applications, drug discovery, telesurgery, and the like.Another application for the sensor-based fluid detection device inengine fluids is an oil/antifreeze monitor, engine diagnostics forair/fuel optimization, diesel fuel quality, volatile organic carbonmeasurement (VOC), fugitive gases in refineries, food quality,halitosis, soil and water contaminants, air quality monitoring, leakdetection, fire safety, chemical weapons identification, use byhazardous material teams, explosive detection, breathalyzers, ethyleneoxide detectors and anaesthetics.

[0093] Biogenic amines such as putrescine, cadaverine, and spermine areformed and degraded as a result of normal metabolic activity in plants,animals and microorganisms, and have been identified and quantifiedusing analytical techniques such as gas chromatography-mass spectrometry(GC-MS), high performance liquid chromatography (HPLC) or array basedvapor sensing in order to assess the freshness of foodstuffs such asmeats (Veciananogues, 1997, J. Agr. Food Chem., 45:2036-2041), cheeses,alcoholic beverages, and other fermented foods. Additionally, anilineand o-toluidine have been reported to be biomarkers for subjects havinglung cancer (Preti et al., 1988, J. Chromat. Biomed. Appl. 432:1-11),while dimethylamine and trimethylamine have been reported to be thecause of the “fishy” uremic breath odor experienced by patients withrenal failure.(Simenhoff, 1977, New England J. Med., 297:132-135) Thus,in general biogenic amines and thiols are biomarkers of bacteria,disease states, food freshness, and other odor-based conditions. Thus,the electronic nose sensor elements and arrays discussed herein can beused to monitor the components in the headspace of urine, blood, sweat,and saliva of human patients, as well as breath, to diagnose variousstates of health and disease. In addition, they can be used for foodquality monitoring, such as fish freshness (which involves volatileamine signatures), for environmental and industrial applications (oilquality, water quality, air quality and contamination and leakdetection), for other biomedical applications, for law enforcementapplications (breathalyzers), for confined space monitoring (indoor airquality, filter breakthrough, etc) and for other applications delineatedabove to add functionality and performance to sensor arrays throughimprovement in analyte detection by use in arrays that combine sensormodalities. For example, surface acoustic wave (SAW) arrays, quartzcrystal microbalance arrays, composites consisting of regions ofconductors and regions of insulators, bulk semiconducting organicpolymers, and other array types exhibit improved performance towardsvapor discrimination and quantification when designed according to theinvention by directing the analyte through, towards or increase contactof the analyte with a sensor (e.g., wherein the array of sensorscomprises a member selected from the group consisting of a metal oxidegas sensor, a conducting polymer sensor, a dye-impregnated polymer filmon fiber optic detector, a polymer-coated micromirror, anelectrochemical gas detector, a chemically sensitive field-effecttransistor, a carbon black-polymer composite, a micro-electro-mechanicalsystem device and a micro-opto-electro-mechanical system device).

[0094] Breath testing has long been recognized as a nonintrusive medicaltechnique that might allow for the diagnosis of disease by linkingspecific volatile organic vapor metabolites in exhaled breath to medicalconditions (see Table 2). In addition to breath analysis beingnonintrusive, it offers several other potential advantages in certaininstances, such as 1) breath samples are easy to obtain, 2) breath is ingeneral a much less complicated mixture of components than either serumor urine samples, 3) direct information can be obtained on therespiratory function that is not readily obtainable by other means, and4) breath analysis offers the potential for direct real time monitoringof the decay of toxic volatile substances in the body. Table 2 listssome of the volatile organic compounds that have been identified astargets for specific diseases using gas chromatography/mass spectrometry(GC/MS) methods, with emphasis on amines. TABLE 2 Patient DiagnosisTarget VOCs VOC Source Uremia; Preti, dimethylamine, trimethylaminebreath, urine 1992; Simenhoff, 1977; Davies, 1997 Trimethylaminuria;trimethylamine breath, urine, Preti, 1992; Alwaiz, sweat, vaginal 1989discharge Lung Cancer; Preti, aniline, o-toluidine lung air 1992Dysgeusia/Dysosmia; hydrogen sulfide, methyl lung air Preti, 1992;Oneill, mercaptan, pyridine, aniline, 1988 diphenylamine, dodecanolCystinuria; Manolis cadaverine, piperidine, breath A., 1983, Clin. Chem.putrescine, pyrrolidine 29:5. Halitosis; Kozlovsky, hydrogen sulfide,methyl mouth air 1994; Preti, 1992 mercaptan, cadaverine, putrescine,indole, skatole Bacterial Vaginosis; amines vaginal cavity Chandiok,1997, J. and discharge Clinical Path., 50:790.

[0095] The invention is described with reference to resistive sensors.Although the invention is described with reference to chemical resistivesensors other types of sensors are applicable to the inventionincluding, for example, heated metal oxide thin film resistors, polymersorption layers on the surfaces of acoustic wave resonators, arrays ofelectrochemical detectors, conductive polymers or composites thatconsist of regions of conductors and regions of insulating organicmaterials and quartz crystal microbalance arrays.

[0096] The sensors and sensor arrays comprise a plurality of differentlyresponding chemical sensors. In one embodiment, the array has at leastone sensor comprising at least a first and second conductive leadelectrically coupled to and separated by a chemically sensitiveresistor. The leads may be any convenient conductive material, usually ametal, and may be interdigitized to maximize signal-to-noise strength.

[0097] In a conductive sensor array (other types of sensor may be used),the array is composed of a material comprising regions of an organicelectrical conductor with regions of a compositionally dissimilarmaterial that is an electrical conductor. The conductive sensor forms aresistor comprising a plurality of alternating regions of differingcompositions and therefore differing conductivity transverse to theelectrical path between the conductive leads. Generally, at least one ofthe sensors is fabricated by blending a conductive material with aconductive organic material. For example, in a colloid, suspension ordispersion of particulate conductive material in a region of conductiveorganic material, the regions separating the particles provide changesin conductance relative to the conductance of the particles themselves.The gaps of different conductance arising from the organic conductivematerial range in path length from about 10 to 1,000 angstroms, usuallyon the order of 100 angstroms. The path length and resistance of a givengap is not constant but rather is believed to change as the materialabsorbs, adsorbs or imbibes an analyte. Accordingly the dynamicaggregate resistance provided by these gaps in a given resistor is afunction of analyte permeation of the conductive organic regions of thematerial. In some embodiments, the conductive material may alsocontribute to the dynamic aggregate resistance as a function of analytepermeation (e.g., when the conductive material is a conductive organicpolymer such as polypyrrole and is blended with another organicconducting material to form the composite).

[0098] A wide variety of conductive materials and dissimilar conductiveorganic materials can be used. In one embodiment, one such region iscomprised of an inorganic (Au, Ag) or organic (carbon black) conductivematerial, while the other region is comprised of a compositionallydissimilar organic conducting polymer (polyaniline, polypyrrole,polythiophene, polyEDOT, and other conducting organic polymers such asthose identified in the Handbook of Conducting Polymers (Handbook ofConducting Polymers, second ed., Marcel Dekker, New York 1997, vols. 1 &2)). Other combinations of conductor/organic conductor/compositematerials are also useful.

[0099] In one implementation, an electrically conductive organicmaterial that is dopable or undopable by protons can be used as theorganic material in a composite where the compositionally differentconductor is carbon black.

[0100] Polyaniline is a desirable member in the class of conductingpolymers in that the half oxidized form, the emeraldine base (y=0.5), isrendered electrically conductive upon incorporation of a strong acid.The conductive form of polyaniline, commonly referred to as theemeraldine salt (ES), has been reported to deprotonate to the emeraldinebase and become insulating in alkaline environments.

[0101] Conductive materials for use in sensor fabrication can include,for example: organic conductors, such as conducting polymers (e.g.,poly(anilines), poly(thiophenes), poly(pyrroles), poly(aceylenes),etc.), carbonaceous material (e.g., carbon blacks, graphite, coke, C60,etc.), charge transfer complexes(tetramethylparaphenylenediamine-chloranile, alkali metaltetracyanoquinodimethane complexes, tetrathiofulvalene halide complexes,etc.), and the like; inorganic conductors, such as metals/metal alloys(e.g., Ag, Au, Cu, Pt, AuCu alloy, etc.), highly doped semiconductors(e.g., Si, GaAs, InP, MoS₂, TiO₂, etc.), conductive metal oxides (e.g.,In₂O₃, SnO₂, Na₂Pt₃O₄, etc.), superconductors (e.g., YBa₂Cu₃O₇,Ti₂Ba₂Ca₂Cu₃O₁₀, etc.), and the like; and mixed inorganic/organicconductors, such as tetracyanoplatinate complexes, iridium halocarbonylcomplexes, stacked macrocyclic complexes, and the like. Blends, such asof those listed, may also be used. Typically conductors include, forexample, those having a positive temperature coefficient of resistance.The sensors are comprised of a plurality of alternating regions of aconductor with regions of a compositionally dissimilar conductingorganic material. Without being bound to any particular theory, it isbelieved that the electrical pathway that an electrical charge traversesbetween the two contacting electrodes traverses both the regions of theconductor and the regions of the organic material. In these embodiments,the conducting region can be anything that can carry electrons from atomto atom, including, but not limited to, a material, a particle, a metal,a polymer, a substrate, an ion, an alloy, an organic material, (e.g.,carbon, graphite, etc.) an inorganic material, a biomaterial, a solid, aliquid, a gas or regions thereof

[0102] In certain other embodiments, the conductive material is aconductive particle, such as a colloidal nanoparticle. As used hereinthe term “nanoparticle” refers to a conductive cluster, such as a metalcluster, having a diameter on the nanometer scale. Such nanoparticlesare optionally stabilized with organic ligands. Examples of colloidalnanoparticles for use in accordance with the present invention aredescribed in the literature. In this embodiment, the electricallyconductive organic region can optionally be a ligand that is attached toa central core making up the nanoparticle. These ligands i.e., caps, canbe polyhomo- or polyhetero-functionalized, thereby being suitable fordetecting a variety of chemical analytes. The nanoparticles, i.e.,clusters, are stabilized by the attached ligands. In certainembodiments, the conducting component of the resistors are nanoparticlescomprising a central core conducting element and an attached ligandoptionally in a polymer matrix. With reference to Table 2, variousconducting materials are suitable for the central core. In certainpreferred embodiments, the nanoparticles have a metal core. Typicalmetal cores include, but are not limited to, Au, Ag, Pt, Pd, Cu, Ni,AuCu and mixtures thereof. These metallic nanoparticles can besynthesized using a variety of methods. In a one method of synthesis, amodification of the protocol developed by Brust et al. can be used.(see, Brust, M.; Walker, M.; Bethell, D.; Schiffrin, D. J.; Whyman, R.J. Chem. Soc., Chem. Commun., 1994, 801-802.) As explained more fullybelow, by varying the concentration of the synthetic reagents, theparticle size can be manipulated and controlled.

[0103] The conductive organic material can be either an organicsemiconductor or organic conductor. “Semi-conductors” as used herein,include materials whose electrical conductivity increases as thetemperature increases, whereas conductors are materials whose electricalconductivity decreases as the temperature increases. By this fundamentaldefinition, organic materials that are useful in some embodiments of thesensors of the present invention are either semiconductors orconductors. Such materials are collectively referred to herein aselectrically conducting organic materials because they produce areadily-measured resistance between two conducting leads separated byabout 10 micron or more using readily-purchased multimeters havingresistance measurement limits of 100 Mohm or less, and thus allow thepassage of electrical current through them when used as elements in anelectronic circuit at room temperature. Semi-conductors and conductorscan be differentiated from insulators by their different roomtemperature electrical conductivity values. Insulators show very lowroom temperature conductivity values, typically less than about 10⁻⁸ohm⁻¹ cm⁻¹. Poly(styrene), poly(ethylene), and other polymers provideexamples of insulating organic materials. Metals have very high roomtemperature conductivities, typically greater than about 10 ohm⁻¹ cm⁻¹.Semi-conductors have conductivities greater than those of insulators,and are distinguished from metals by their different temperaturedependence of conductivity, as described above. The organic materialsthat are useful in an embodiment of the sensors of the invention areeither electrical semiconductors or conductors, and have roomtemperature electrical conductivities of greater than about 10⁻⁶ ohm⁻¹cm⁻¹, typically having a conductivity of greater than about 10⁻³ ohm⁻¹cm⁻¹.

[0104] Accordingly, the sensors of the invention can include sensorscomprising regions of an electrical conductor and regions of acompositionally different organic material that is an electricalconductor or semiconductor. As used above, electrical conductorsinclude, for example, Au, Ag, Pt and carbon black, other conductivematerials having similar resistivity profiles are easily identified inthe art (see, for example the latest edition of: The CRC Handbook ofChemistry and Physics, CRC Press, the disclosure of which isincorporated herein by reference). Furthermore, insulators can also beincorporated into the composite to further manipulate the analyteresponse properties of the composites. The insulating region (i.e.,non-conductive region) can be anything that can impede electron flowfrom atom to atom, including, but not limited to, a material, a polymer,a plasticizer, an organic material, an organic polymer, a filler, aligand, an inorganic material, a biomaterial, a solid, a liquid, a gasand regions thereof. Insulating organic materials that can be used forsuch purposes can include, for example: main-chain carbon polymers, suchas poly(dienes), poly(alkenes), poly(acrylics), poly(methacrylics),poly(vinyl ethers), poly(vinyl thioethers), poly(vinyl alcohols),poly(vinyl ketones), poly(vinyl halides), poly(vinyl nitrites),poly(vinyl esters), poly(styrenes), poly(aryines), and the like;main-chain acyclic heteroatom polymers, such as poly(oxides),poly(caronates), poly(esters), poly(anhydrides), poly(urethanes),poly(sulfonate), poly(siloxanes), poly(sulfides), poly(thioesters),poly(sulfones), poly(sulfonamindes), poly(amides), poly(ureas),poly(phosphazens), poly(silanes), poly(silazanes), and the like; andmain-chain heterocyclic polymers, such as poly(furantetracarboxylic aciddiimides), poly(benzoxazoles), poly(oxadiazoles),poly(benzothiazinophenothiazines), poly(benzothiazoles),poly(pyrazinoquinoxalines), poly(pyromenitimides), poly(quinoxalines),poly(benzimidazoles), poly(oxidoles), poly(oxoisinodolines),poly(diaxoisoindoines), poly(triazines), poly(pyridzaines),poly(pioeraziness), poly(pyridines), poly(pioeridiens), poly(triazoles),poly(pyrazoles), poly(pyrrolidines), poly(carboranes),poly(oxabicyclononanes), poly(diabenzofurans), poly(phthalides),poly(acetals), poly(anhydrides), carbohydrates, and the like.

[0105] Nonconductive organic polymer materials; blends and copolymers;plasticized polymers; and other variations including those using thepolymers listed here, may also be used. Combinations, concentrations,blend stoichiometries, percolation thresholds, etc. are readilydetermined empirically by fabricating and screening prototype resistors(chemiresistors) as described below.

[0106] The chemiresistors can be fabricated by many techniques such as,but not limited to, solution casting, suspension casting, and mechanicalmixing. In general, solution cast routes are advantageous because theyprovide homogeneous structures and ease of processing. With solutioncast routes, sensor elements may be easily fabricated by spin, spray ordip coating. Suspension casting still provides the possibility of spin,spray or dip coating but more heterogeneous structures than withsolution casting are expected. With mechanical mixing, there are nosolubility restrictions since it involves only the physical mixing ofthe resistor components, but device fabrication is more difficult sincespin, spray and dip coating are no longer possible.

[0107] For systems where both the conducting, compositionally dissimilarorganic conducting and non-conducting material or their reactionprecursors are soluble in a common solvent, the chemiresistors can befabricated by solution casting. The oxidation of pyrrole byphosphomolybdic acid represents such a system. In this reaction, thephosphomolybdic acid and pyrrole are dissolved in tetrahydrofuran (THF)and polymerization occurs upon solvent evaporation. This allows for THFsoluble compositionally different conductive, semiconductive, andnon-conductive materials to be dissolved into this reaction regionthereby allowing the composite to be formed in a single step uponsolvent evaporation.

[0108] A variety of permutations on this scheme are possible for otherconducting polymers. Some of these are listed below. Certain conductingorganic polymers, such as substituted poly-(cyclooctatetraenes), aresoluble in their undoped, non-conducting state in solvents such as THFor acetonitrile. Consequently, the blends between the undoped polymerand other organic materials can be formed from solution casting. Afterwhich, the doping procedure (exposure to I₂ vapor, for instance) can beperformed on the blend to render the substituted poly(cyclooctatetraene)conductive. Again, the choice of compositionally different organicmaterials is limited to those that are soluble in the solvents that theundoped conducting polymer is soluble in and to those stable to thedoping reaction.

[0109] Certain conducting organic polymers can also be synthesized via asoluble precursor polymer. In these cases, blends between the precursorpolymer and the compositionally different material of the composite canfirst be formed followed by chemical reaction to convert the precursorpolymer into the desired conducting polymer. For instancepoly(p-phenylene vinylene) can be synthesized through a solublesulfonium precursor. Blends between this sulfonium precursor and anon-conductive or conductive polymer can be formed by solution casting.After which, the blend can be subjected to thermal treatment undervacuum to convert the sulfonium precursor to the desiredpoly(p-phenylene vinylene).

[0110] In suspension casting, one or more of the components of thesensor is suspended and the others dissolved in a common solvent.Suspension casting is a rather general technique applicable to a widerange of species, such as carbon blacks or colloidal metals, which canbe suspended in solvents by vigorous mixing or sonication. In oneapplication of suspension casting, the conductive organic or conductivepolymer is dissolved in an appropriate solvent (such as THF,acetonitrile, water, etc.). Carbon black is then suspended in thissolution and the resulting region is used to dip coat or spray coatelectrodes.

[0111] Mechanical mixing is suitable for all of theconductive/conductive organic/non-conductive combinations possible. Inthis technique, the materials are physically mixed in a ball-mill orother mixing device. For instance, carbon black/conducting organicpolymer composites are readily made by ball-milling. When thesemiconductive or conductive organic material can be melted orsignificantly softened without decomposition, mechanical mixing atelevated temperature can improve the mixing process. Alternatively,composite fabrication can sometimes be improved by several sequentialheat and mix steps.

[0112] Once fabricated, the individual sensors can be optimized for aparticular application by varying their chemical make up andmorphologies. The chemical nature of the sensors determines to whichanalytes they will respond and their ability to distinguish differentanalytes. The relative ratio of conductive to compositionally differentorganic conductive or semiconductive organic material, along with thecomposition of any other insulating organic or inorganic components, candetermine the magnitude of the response since the resistance of theelements becomes more sensitive to sorbed molecules as the percolationthreshold is approached and as the molecules interact chemically withthe components of the composite that adsorb or absorb the analyte. Thefilm morphology is also important in determining responsecharacteristics. For instance, uniform thin films respond more quicklyto analytes than do uniform thick ones. However, it may be advantageousto include sensors of varying thickness to determine various diffusioncoefficients or other physical characteristics of the analyte beinganalyzed. Hence, with an empirical catalogue of information onchemically diverse sensors made with varying ratios of semiconductive,conducting, and insulating components and by differing fabricationroutes, sensors can be chosen that are appropriate for the analytesexpected in a particular application, their concentrations, and thedesired response times. Further optimization can then be performed in aniterative fashion as feedback on the performance of an array underparticular conditions becomes available.

[0113] The resistor may itself form a substrate for attaching the leador the resistor. For example, the structural rigidity of the resistorsmay be enhanced through a variety of techniques: chemical or radiationcross-linking of polymer components (dicumyl peroxide radicalcross-linking, UV-radiation cross-linking of poly(olefins), sulfurcross-linking of rubbers, e-beam cross-linking of Nylon, etc.), theincorporation of polymers or other materials into the resistors toenhance physical properties (for instance, the incorporation of a highmolecular weight, high melting temperature (T_(m)) polymers), theincorporation of the resistor elements into supporting matrices such asclays or polymer networks (forming the resistor blends withinpoly-(methylmethacrylate) networks or within the lamellae ofmontmorillonite, for instance), etc. In another embodiment, the resistoris deposited as a surface layer on a solid matrix which provides meansfor supporting the leads. As described above, these supporting matricescan be porous or permeable to certain analytes across which a pressuredifference is created to effectuate analyte contact with the sensor.

[0114] Sensor arrays particularly well suited to scaled up productionare fabricated using integrated circuit (IC) design technologies. Forexample, the chemiresistors can easily be integrated onto the front endof a simple amplifier interfaced to an A/D converter to efficiently feedthe data stream directly into a neural network software or hardwareanalysis section. Micro-fabrication techniques can integrate thechemiresistors directly onto a micro-chip which contains the circuitryfor analog signal conditioning/processing and then data analysis. Thisprovides for the production of millions of incrementally differentsensor elements in a single manufacturing step using ink-jet technology.Controlled compositional gradients in the chemiresistor elements of asensor array can be induced in a method analogous to how a color ink-jetprinter deposits and mixes multiple colors. However, in this case ratherthan multiple colors, a plurality of different organic materials andconducting components suspended or dissolved in solution which can bedeposited are used. A sensor array of a million distinct elements onlyrequires a 1 cm×1 cm sized chip employing lithography at the 10micrometer feature level, which is within the capacity of conventionalcommercial processing and deposition methods. This technology permitsthe production of sensitive, small-sized, stand-alone chemical sensors.

[0115] In one embodiment, the sensor arrays have a predeterminedinter-sensor variation in the structure or composition of the conductiveor semiconductive or insulating organic materials as well as in theconductive components and any insulating or plasticizing components ofthe composites. The variation may be quantitative and/or qualitative.For example, the concentration of the conductive or semiconductive orinsulating organic material in the composite can be varied acrosssensors. Alternatively, a variety of different organic materials may beused in different sensors. The anions that accompany conducting orsemiconducting organic polymers such as polyaniline in some dopingstates can be compositionally varied to add diversity to the array, ascan the polymer composition itself, either structurally (through use ofa different family of materials) or through modification of the backboneand/or side chains of the basic polymer structure. This ability tofabricate many chemically different materials allows ready incorporationof a wide range of chemical diversity into the sensor elements, and alsoallows facile control over the electrical properties of the sensorelements through control over the composition of an individual sensorelement in the array. Insulating organic materials can also be used andblended into the array in order to further increase the diversity in oneembodiment of the invention. When insulators are added, commercial,off-the-shelf, organic polymers can provide the basic sensor componentsthat respond differently to different analytes, based on the differencesin polarity, molecular size, and other properties of the analyte inorder to achieve the chemical diversity amongst array elements in theelectronic nose sensors. Such insulators would include main-chain carbonpolymers, main chain acyclic heteroatom polymers, main-chainheterocyclic polymers, and other insulating organic materials.Otherwise, these properties can be obtained by modification in thecomposition of the electrically conductive or electricallysemiconductive organic component of the sensor composition by use ofcapping agents on a colloidal metal part of the conductive phase, by useof different plasticizers added to otherwise compositionally identicalsensor elements to manipulate their analyte sorption and responseproperties, by variation in the temperature or measurement frequency ofthe sensors in an array of sensors that are otherwise compositionallyidentical, or a combination thereof and with sensors that arecompositionally different as well. The sensors in an array can readilybe made by combinatorial methods in which a limited number of feedstocksis combined to produce a large number of chemically distinct sensorelements.

[0116] One method of enhancing the diversity of polymer basedconductor/conductor or conductor/semiconductor or conductor/insulatorchemiresistors is through the use of polymer blends or copolymers(Doleman, et al. (1998) Anal. Chem. 70, 2560-2654). Immiscible polymerblends may also be of interest because carbon black or other conductorscan be observed to preferentially segregate into one of the blendcomponents. Such a distribution of carbon black conduction pathways mayresult in valuable effects upon analyte sorption, such as the observanceof a double percolation threshold. Binary polymer blend sensors can beprepared from a variety of polymers at incrementally different blendstoichiometries. Instead of manually fabricating twenty blends ofvarying composition, a spray gun with dual controlled-flow feedstockscould be used to deposit a graded-composition polymer film across aseries of electrodes. Such automated procedures allow extension of thesensor compositions beyond simple binary blends, thereby providing theopportunity to fabricate chemiresistors with sorption propertiesincrementally varied over a wide range. In the fabrication ofmany-component blends, a combinatorial approach aided by microjetfabrication technology is one approach that will be known to thoseskilled in the art. For instance, a continuous jet fed by five separatefeedstocks can fabricate numerous polymer blends in a combinatorialfashion on substrates with appropriately patterned sets of electrodes.Multiple nozzle drop-on-demand systems (multiple nozzle continuous jetsystems are not as prevalent because of their greater complexity) mayalso be used. In this approach, each nozzle would be fed with adifferent polymer, each dissolved in a common solvent. In this manner, alarge number of combinations of 10-20 polymers can be readilyfabricated.

[0117] The resistors can include nanoparticles comprising a central coreconducting element and an attached ligand, with these nanoparticlesdispersed in a semiconducting or conducting organic matrix. As describedabove, in certain embodiments, the nanoparticles have a metal core. Inone method of synthesizing such a core, a modification of the protocoldeveloped by Brust et al. (the teachings of which are incorporatedherein by reference), can be used. Using alkanethiolate gold clusters asan illustrative example, and not in any way to be construed as limiting,the starting molar ratio of HAuCl₄ to alkanethiol is selected toconstruct particles of the desired diameter. The organic phase reductionof HAuCl₄ by an alkanethiol and sodium borohydride leads to stable,modestly polydisperse, alkanethiolate-protected gold clusters having acore dimension of about 1 nm to about 100 nm. The nanoparticles range insize from about 1 nm to about 50 nm, but may also range in size fromabout 5 nm to about 20 nm.

[0118] In this reaction, a molar ratio of HAuCl₄ to alkanethiol ofgreater than 1:1 leads to smaller particle sizes, whereas a molar ratioof HAuCl₄ to alkanethiol less than 1:1 yield clusters which are largerin size. Thus, by varying the ratio of HAuCl₄ to alkanethiol, it ispossible to generate various sizes and dimensions of nanoparticlessuitable for a variety of analytes. Although not intending to be boundby any particular theory, it is believed that during the chemicalreaction, as neutral gold particles begin to nucleate and grow, the sizeof the central core is retarded by the ligand monolayer in a controlledfashion. Using this reaction, it is then possible to generatenanoparticles of exacting sizes and dimensions.

[0119] In certain other embodiments, sensors are prepared as compositesof “naked” nanoparticles and a semiconducting or conducting organicmaterial is added. As used herein, the term “naked nanoparticles” meansthat the core has no covalently attached ligands or caps. A wide varietyof semiconducting or conducting organic materials can be used in thisembodiment. Preferred semiconducting or conducting materials are organicpolymers. Suitable organic polymers include, but are not limited to,polyaniline, polypyrrole, polyacetylene, polythiophene, polyEDOT andderivatives thereof. Varying the semiconducting or conducting materialtypes, concentration, size, etc., provides the diversity necessary foran array of sensors. In one embodiment, the conductor to semiconductingor conducting organic material ratio is about 50% to about 90% (wt/wt).

[0120] The general method for using the disclosed sensors, arrays andelectronic noses, for detecting the presence of an analyte in a fluid,where the fluid is a liquid or a gas, involves sensing the presence ofan analyte in a fluid with a chemical sensor. In a preferredimplementation, a preferred detector array produces a unique signaturefor every different analyte to which it is expected to be exposed. Suchsystems can be constructed to include detectors that probe important,but possibly subtle, molecular parameters such as chirality. The term“chiral” is used herein to refer to an optically active orenantiomerically pure compound, or to a compound containing one or moreasymmetric centers in a well-defined optically active configuration. Achiral compound is not superimposable upon its mirror image. Harnessingenantiomer resolution gives rise to myriad applications. For instance,because the active sites of enzymes are chiral, only the correctenantiomer is recognized as a substrate. Thus, pharmaceuticals havingnear enantiomeric purity are often many more times active than theirracemic mixtures. However, many pharmaceutical formulations marketedtoday are racemic mixtures of the desired compound and its “mirrorimage.” One optical form (or enantiomer) of a racemic mixture may bemedicinally useful, while the other optical form may be inert or evenharmful, as has been reported to be the case for thalidomide. Variousmethods exist which generate the correct enantiomer, including chiralsynthesis, enzymatic resolution or some other means of obtaining theoptically active compound. Due to the wide range of industrialapplications, there is a growing interest in finding ways to resolveracemic mixtures into optically active isomers, or to synthesizeenantiomerically pure compounds directly and rapidly monitor theefficiency of such processes. Chiral sensor elements could be part of alarger detector array that included non-chiral elements, thus broadeningthe discrimination ability of such arrays towards chiral analytes. Someof the elements can possess chiral feedstocks and/or chiral organicelectrically conducting elements and/or chiral capping agents onconductive particles in order to detect chiral analytes through theirdistinct response pattern on an array of sensors. Suitable chiralresolving agents include, but are not limited to, chiral molecules, suchas chiral polymers; natural products, such as, tartaric, malic andmandelic acids; alkaloids, such as brucine, strychnine, morphine andquinine; lanthanide shift reagents; chelating agents; biomolecules, suchas proteins, cellulose and enzymes; and chiral crown ethers togetherwith cyclodextrins. (see, E. Gassmann et al., “Electrokinetic Separationof Chiral Compounds,” Science, vol. 230, pp. 813-814 (1985); and R. Kuhnet al., “Chiral Separation by Capillary Electrophoresis,”Chromatographia, vol. 34, pp. 505-512 (1992)). Additional chiralresolving agents suitable for use in the present invention will be knownby those of skill in the art. In this fashion, the sensors and sensorarrays can assist in assessing which form of chirality, and of whatenantiomeric excess, is present in an analyte in a fluid. Due to thepresence of chiral moieties, many biomolecules, such as amino acids, areamenable to detection using the sensor arrays of the invention.

[0121] Plasticizers can also be used to obtain improved mechanical,structural, and sorption properties of the sensing films. Suitableplasticizers for use in the present invention include, but are notlimited to, phthalates and their esters, adipate and sebacate esters,polyols such as polyethylene glycol and their derivatives, tricresylphosphate, castor oil, camphor etc. Those of skill in the art will beaware of other plasticizers suitable for use in the present invention.

[0122] The plasticizer can also be added to an organic polymer formingan interpenetrating network (IPN) comprising a first organic polymer anda second organic polymer formed from an organic monomer polymerized inthe presence of the first organic polymer. This technique worksparticularly well when dealing with polymers that are immiscible in oneanother, where the polymers are made from monomers that are volatile.Under these conditions, the preformed polymer is used to dictate theproperties (e.g., viscosity) of the polymer-monomer region. Thus, thepolymer holds the monomer in solution. Examples of such a system are (1)polyvinyl acetate with monomer methylmethacrylate to form an IPN of pVAand pMMA, (2) pVA with monomer styrene to form an IPN of pVA andpolystyrene, and (3) pVA with acrylonitrile to form an IPN of pVA andpolyacrylonitrile. Each of the example compositions would be modified bythe addition of an appropriate plasticizer. More than one monomer can beused where it is desired to create an IPN having one or more copolymers.

[0123] In another embodiment, the sensor for detecting the presence of achemical analyte in a fluid comprises a chemically sensitive resistorelectrically connected to an electrical measuring apparatus where theresistor is in thermal communication with a temperature controlapparatus. As described above, the chemically sensitive resistor(s) maycomprise regions of a conductive organic polymer and regions of aconductive material which is compositionally different than theconductive organic material. The chemically sensitive resistor providesan electrical path through which electrical current may flow and aresistance (R) at a temperature (T) when contacted with a fluidcomprising a chemical analyte.

[0124] In operation, chemically sensitive resistor(s) of the sensor fordetecting the presence of a chemical analyte in a fluid provide anelectrical resistance (R_(m)) when contacted with a fluid comprising achemical analyte at a particular temperature (T_(m)). The electricalresistance observed may vary as the temperature varies, thereby allowingone to define a unique profile of electrical resistances at variousdifferent temperatures for any chemical analyte of interest. Forexample, a chemically sensitive resistor, when contacted with a fluidcomprising a chemical analyte of interest, may provide an electricalresistance R_(m) at temperature T_(m) where m is an integer greater than1, and may provide a different electrical resistance R_(n) at adifferent temperature T_(n). The difference between R_(m) and R_(n) isreadily detectable by an electrical measuring apparatus.

[0125] As such, the chemically sensitive resistor(s) of the sensor arein thermal communication with a temperature control apparatus, therebyallowing one to vary the temperature at which electrical resistances aremeasured. If the sensor comprises an array of two or more chemicallysensitive resistors each being in thermal communication with atemperature control apparatus, one may vary the temperature across theentire array (i.e., generate a temperature gradient across the array),thereby allowing electrical resistances to be measured simultaneously atvarious different temperatures and for various different resistorcompositions. For example, in an array of chemically sensitiveresistors, one may vary the composition of the resistors in thehorizontal direction across the array, such that resistor composition inthe vertical direction across the array remains constant. One may thencreate a temperature gradient in the vertical direction across thearray, thereby allowing the simultaneous analysis of chemical analytesat different resistor compositions and different temperatures.

[0126] Methods for placing chemically sensitive resistors in thermalcommunication with a temperature control apparatus are readily apparentto those skilled in the art and include, for example, attaching aheating or cooling element to the sensor and passing electrical currentthrough said heating or cooling element. The temperature range acrosswhich electrical resistance may be measured will be a function of theresistor composition, for example the melting temperature of theresistor components, the thermal stability of the analyte of interest orany other component of the system, and the like. For the most part, thetemperature range across which electrical resistance will be measuredwill be about 10° C. to 80° C., preferably from about 22° C. to about70° C. and more preferably from about 20° C. to 65° C.

[0127] In yet another embodiment, rather than subjecting the sensor to adirect electrical current and measuring the true electrical resistancethrough the chemically sensitive resistor(s), the sensor can besubjected to an alternating electrical current at different frequenciesto measure impedance. Impedance is the apparent resistance in analternating electrical current as compared to the true electricalresistance in a direct current. As such, the present invention is alsodirected to a sensor for detecting the presence of a chemical analyte ina fluid, said sensor comprising a chemically sensitive resistorelectrically connected to an electrical measuring apparatus, whereinsaid resistor provides (a) an electrical path through said region ofnonconductive organic polymer and said conductive material, and (b) anelectrical impedance Z_(m) at frequency m when contacted with a fluidcomprising said chemical analyte, where m is an integer greater than 1and m does not equal 0. For measuring impedance as a function offrequency, the frequencies employed will generally range from about 1 Hzto 5 GHz, usually from about 1 MHZ to 1 GHz, more usually from about 1MHZ to 10 MHZ and preferably from about 1 MHZ to 5 MHZ. Chemicalanalytes of interest will exhibit unique impedance characteristics atvarying alternating current frequencies, thereby allowing one to detectthe presence of any chemical analyte of interest in a fluid by measuringZ_(m) at alternating frequency m.

[0128] For performing impedance measurements, one may employ virtuallyany impedance analyzer known in the art. For example, a SchlumbergerModel 1260 Impedance/Gain-Phase Analyzer (Schlumberger Technologies,Farmborough, Hampshire, England) with approximately 6 inch RG174 coaxialcables is employed. In such an apparatus, the resistor/sensor is held inan A1 chassis box to shield it from external electronic noise.

[0129] In still another embodiment of the present invention, one mayvary both the frequency m of the electrical current employed and thetemperature T_(n) and measure the electrical impedance Z_(m,n), therebyallowing for the detection of the presence of a chemical analyte ofinterest. As such, the present invention is also directed to a sensorfor detecting the presence of a chemical analyte in a fluid, said sensorcomprising a chemically sensitive resistor electrically connected to anelectrical measuring apparatus and being in thermal communication with atemperature control apparatus, wherein said resistor provides anelectrical impedance Z_(m,n) at frequency m and temperature T_(n) whencontacted with a fluid comprising said chemical analyte, where m and/orn is an integer greater than 1. For measuring impedance as a function offrequency and temperature, the frequencies employed will generally notbe higher than 10 MHZ, preferably not higher than 5 MHZ. Chemicalanalytes of interest will exhibit unique impedance characteristics atvarying alternating current frequencies and varying temperatures,thereby allowing one to detect the presence of any chemical analyte ofinterest in a fluid by measuring Z_(m,n) at frequency m and temperatureT_(n).

[0130] In another procedure, one particular sensor composition can beused in an array and the response properties can be varied bymaintaining each sensor at a different temperature from at least one ofthe other sensors, or by performing the electrical impedance measurementat a different frequency for each sensor, or a combination thereof.

[0131] Electronic noses (such as system 100, above) for detecting ananalyte in a fluid can be fabricated by electrically coupling the sensorleads of an array of differently responding sensors to an electricalmeasuring device (e.g., detector 180). The device measures changes insignal at each sensor of the array, preferably simultaneously andpreferably over time. Preferably, the signal is an electricalresistance, although it could also be an impedance or other physicalproperty of the material in response to the presence of the analyte inthe fluid. Frequently, the device includes signal processing means andis used in conjunction with a computer and data structure for comparinga given response profile to a structure-response profile database forqualitative and quantitative analysis. Typically, the array includesusually at least ten, often at least 100, and perhaps at least 1000different sensors though with mass deposition fabrication techniquesdescribed herein or otherwise known in the art, arrays of on the orderof at least one million sensors are readily produced.

[0132] In one mode of operation with an array of sensors, each resistorprovides a first electrical resistance between its conductive leads whenthe resistor is contacted with a first fluid comprising a first chemicalanalyte, and a second electrical resistance between its conductive leadswhen the resistor is contacted with a second fluid comprising a second,different, chemical analyte. The fluids may be liquid or gaseous innature. The first and second fluids may reflect samples from twodifferent environments, a change in the concentration of an analyte in afluid sampled at two time points, a sample and a negative control, etc.The sensor array necessarily comprises sensors which respond differentlyto a change in an analyte concentration or identity, i.e., thedifference between the first and second electrical resistance of onesensor is different from the difference between the first secondelectrical resistance of another sensor.

[0133] In one embodiment, the temporal response of each sensor(resistance as a function of time) is recorded. The temporal response ofeach sensor may be normalized to a maximum percent increase and percentdecrease in signal which produces a response pattern associated with theexposure of the analyte. By iterative profiling of known analytes, astructure-function database correlating analytes and response profilesis generated. Unknown analytes may then be characterized or identifiedusing response pattern comparison and recognition algorithms.Accordingly, analyte detection systems comprising sensor arrays, anelectrical measuring device for detecting resistance across eachchemiresistor, a computer, a data structure of sensor array responseprofiles, and a comparison algorithm are provided. In anotherembodiment, the electrical measuring device is an integrated circuitcomprising neural network-based hardware and a digital-analog converter(DAC) multiplexed to each sensor, or a plurality of DACs, each connectedto different sensor(s).

[0134] The desired signals if monitored as dc electrical resistances forthe various sensor elements in an array can be read merely by imposing aconstant current source through the resistors and then monitoring thevoltage across each resistor through use of a commercial multiplexable20 bit analog-to-digital converter. Such signals are readily stored in acomputer that contains a resident algorithm for data analysis andarchiving. Signals can also be preprocessed either in digital or analogform; the latter might adopt a resistive grid configuration, forexample, to achieve local gain control. In addition, long timeadaptation electronics can be added or the data can be processeddigitally after it is collected from the sensors themselves. Thisprocessing could be on the same chip as the sensors but also couldreside on a physically separate chip or computer.

[0135] Data analysis can be performed using standard chemometric methodssuch as principal component analysis and SIMCA, which are available incommercial software packages that run on a PC or which are easilytransferred into a computer running a resident algorithm or onto asignal analysis chip either integrated onto, or working in conjunctionwith, the sensor measurement electronics. The Fisher linear discriminantis one preferred algorithm for analysis of the data, as described below.In addition, more sophisticated algorithms and supervised orunsupervised neural network based learning/training methods can beapplied as well (Duda, R. O.; Hart, P. E. Pattern Classification andScene Analysis; John Wiley & Sons: New York, 1973, pp 482).

[0136] The signals can also be useful in forming a digitallytransmittable representation of an analyte in a fluid. Such signalscould be transmitted over the Internet in encrypted or in publiclyavailable form and analyzed by a central processing unit at a remotesite, and/or archived for compilation of a data set that could be minedto determine, for example, changes with respect to historical mean“normal” values of the breathing air in confined spaces, of human breathprofiles, and of a variety of other long term monitoring situationswhere detection of analytes in fluids is an important value-addedcomponent of the data.

[0137] Arrays of 20 to 30 different sensors may be sufficient for manyanalyte classification tasks but larger array sizes can be implementedas well. Temperature and humidity can be controlled but because apreferred mode is to record changes relative to the ambient baselinecondition, and because the patterns for a particular type andconcentration of odorant are generally independent of such baselineconditions, it is not critical to actively control these variables insome implementations of the technology. Where desired, such control canbe achieved either in open-loop or closed-loop configurations.

[0138] The sensors and sensor arrays disclosed herein can be used withor without preconcentration of the analyte depending on the power levelsand other system constraints demanded by the user. Regardless of thesampling mode, the characteristic patterns (both from amplitude andtemporal features, depending on the most robust classification algorithmfor the purpose) associated with certain disease states and othervolatile analyte signatures can be identified using the sensorsdisclosed herein. These patterns are then stored in a library, andmatched against the signatures emanating from the sample to determinethe likelihood of a particular odor falling into the category of concern(disease or nondisease, toxic or nontoxic chemical, good or bad polymersamples, fresh or old fish, fresh or contaminated air, etc.).

[0139] Analyte sampling will occur differently in the variousapplication scenarios. For some applications, direct headspace samplescan be collected using either single breath and urine samples in thecase of sampling a patient's breath for the purpose of disease or healthstate differentiation and classification. In addition, extended breathsamples, passed over a Tenax, Carbopack, Poropak, Carbosieve, or othersorbent preconcentrator material, can be obtained when needed to obtainrobust intensity signals. Suitable commercially available adsorbentmaterials include but are not limited to, Tenax TA, Tenax GR, Carbotrap,Carbopack B and C, Carbotrap C, Carboxen, Carbosieve SIII, Porapak,Spherocarb, and combinations thereof. Preferred adsorbent combinationsinclude, but are not limited to, Tenax GR and Carbopack B; Carbopack Band Carbosieve SIII; and Carbopack C and Carbopack B and Carbosieve SIIIor Carboxen 1000. Those skilled in the art will know of other suitableabsorbent materials.

[0140] The analyte can be concentrated from an initial sample volume ofabout 10 liters and then desorbed into a concentrated volume of about 10milliliters or less, before being presented to the sensor array. Theabsorbent material of the fluid concentrator can be, but is not limitedto, a nanoporous material, a microporous material, a chemically reactivematerial, a nonporous material and combinations thereof. In certaininstances, the absorbent material can concentrate the analyte by afactor that exceeds a factor of about 10⁵, or by a factor of about 10²to about 10⁴. In another embodiment, removal of background water vaporis conducted in conjunction, such as concomitantly, with theconcentration of the analyte. Once the analyte is concentrated, it canbe desorbed using a variety of techniques, such as heating, purging,stripping, pressuring or a combination thereof. In some theseembodiments, the sample concentrator can be wrapped with a wire throughwhich current can be applied to heat and thus, desorb the concentratedanalyte. The analyte is thereafter transferred to the sensor array.

[0141] Breath samples can be collected through a straw or suitable tubein a patient's mouth that is connected to the sample chamber (orpreconcentrator chamber), with the analyte outlet available for captureto enable subsequent GC/MS or other selected laboratory analyticalstudies of the sample. In other applications, headspace samples ofodorous specimens can be analyzed and/or carrier gases can be used totransmit the analyte of concern to the sensors to produce the desiredresponse. In still other cases, the analyte will be in a liquid phaseand the liquid phase will be directly exposed to the sensors; in othercases the analyte will undergo some separation initially and in yetother cases only the headspace of the analyte will be exposed to thesensors.

[0142] In some cases, the array will not yield a distinct signature ofeach individual analyte in a region, unless one specific type of analytedominates the chemical composition of a sample. Instead, a pattern thatis a composite, with certain characteristic temporal features of thesensor responses that aid in formulating a unique relationship betweenthe detected analyte contents and the resulting array response, will beobtained.

[0143] In a preferred embodiment of signal processing, the Fisher lineardiscriminant searches for the projection vector, w, in the detectorspace which maximizes the pairwise resolution factor, i.e., rf, for eachset of analytes, and reports the value of rf along this optimal lineardiscriminant vector. The rf value is an inherent property of the dataset and does not depend on whether principal component space or originaldetector space is used to analyze the response data. This resolutionfactor is basically a multi-dimensional analogue to the separationfactors used to quantify the resolving power of a column in gaschromatography, and thus the if value serves as a quantitativeindication of how distinct two patterns are from each other, consideringboth the signals and the distribution of responses upon exposure to theanalytes that comprise the solvent pair of concern. For example,assuming a Gaussian distribution relative to the mean value of the datapoints that are obtained from the responses of the array to any givenanalyte, the probabilities of correctly identifying an analyte as a or bfrom a single presentation when a and b are separated with resolutionfactors of 1.0, 2.0 or 3.0 are approximately 76%, 92% and 98%respectively.

[0144] The following examples are offered by way of illustration and notby way of limitation.

EXAMPLES

[0145] Polymers, including poly (ethylene-co-vinyl acetate) with 25%acetate (PEVA), and poly(caprolactone) (PCL) were purchased fromScientific Polymer Products. Solvents were purchased from AldrichChemical Corp or EM Science and were used as received.

[0146] Detector Film Fabrication. Carbon black-polymer compositesuspensions used to form the detector films were prepared by dissolving160 mg of polymer in toluene, followed by addition of 40 mg of carbonblack (Cabot Black Pearls 2000) (Lonergan, et al., Chem. Mat. 1996, 8,2298-2312). The mixtures were sonicated for 10 min and were then sprayedin several lateral passes using an airbrush (Iowata HP-BC) held at adistance of 10 to 14 cm from the substrate.

[0147] Vapor Flow Apparatus. An automated flow system was used todeliver pulses of a diluted stream of solvent vapor to the detectors(Doleman, et al., Anal. Chem. 1998, 70, 2560-2564). The carrier gas wasoil-free air obtained from the house compressed air source (1.10±0.15parts per thousand (ppth) of water vapor) controlled with a 28 L min⁻¹or a 625 ml min⁻¹ mass flow controller (UNIT). To obtain the desiredconcentration of analyte in the gas phase, a stream of carrier gascontrolled by a 625 ml min⁻¹ or a 60 ml min⁻¹ mass flow controller waspassed though one of five bubblers. Saturation of the gas flow throughthe bubbler of interest was confirmed with a flame ionization detector(Model 300 HFID, California Analytical Instruments, Inc.). The saturatedgas stream was then mixed with background air to produce the desiredanalyte concentration while maintaining the total air flow at thedesired value for the linear flow chamber experiments (Example 3, below)and at a constant value of 2 L min⁻¹ for the stacked detector assemblies(Example 4).

[0148] For detectors in the linear flow chamber, the air flow wasconnected directly to the channel adjacent to the row of detectors. Toproduce the low flow rates required by this experiment, theanalyte-containing vapor was generated at higher flow rates, and aconstant 200 ml min⁻¹ was subtracted with a flow-regulated pump,permitting the difference to flow into the detector chamber. This flowwas then divided into the two equally sized openings of the two channelsin the chamber. The volumetric flow rates quoted below reflect thevolumetric flow rate in each separate gap between the detector substrateand the Teflon-lined A1 block.

[0149] For detectors arranged in the stacked assembly, a constant outputof 2 L min⁻¹ from the vapor generator was directed at the front end ofthe sampling device through use of a Teflon tube that was slightlylarger in diameter than the opening of the stack device. Vapor flowthrough the channels in the stack assembly was maintained at avolumetric flow rate of 75 ml min⁻¹, i.e., 12.5 ml min⁻¹ per channel.The excess flow of 1.925 L min⁻¹ flowed away from the stack devicewithout proceeding through the channels or over the face sensors.

[0150] All exposed parts of the flow system were constructed fromTeflon, stainless steel, or A1. The temperature during data collectionwas approximately 294 K, and the temperature was passively controlled byimmersing the solvent bubblers into large tanks of water. For the linearrow of detectors, vapor presentations were 300 s in duration, andanalyte exposures were separated in time by at least 75 min to minimizeany possible influence of the previous exposure. The analyte wasdelivered at a constant activity of P/P^(o)=0.10, where P is the partialpressure and P^(o) is the vapor pressure of the analyte. For experimentswith stacked detector arrays, the vapor presentations were 240 s induration, separated in time by 25 min, and were conducted at a fixedanalyte activity of P/P^(o)=0.050. Flow experiments were performedseparately on each of the three separate stack assemblies. Each stackassembly received 10 exposures to each of four analytes, and the orderof these 40 total presentations was randomized with respect to theanalyte identity and with respect to replicate exposures to a givenanalyte. A different randomized analyte presentation order was used foreach of the three stack assemblies. A personal computer running programsdeveloped with LabVIEW 5.0 controlled both the flow system and the dataacquisition apparatus.

[0151] DC Resistance Measurements. DC resistance data were collectedusing a Keithley 2002 multimeter and a Keithley 7001 multiplexer.Shielded, twisted pair cables were used, and each resistance value wasintegrated over 2 or 10 power line cycles to reject 60 Hz pickup. Datawere processed using a program written in Microsoft Excel Basic. Therelative differential resistance change, ΔR_(final)/R_(b), wascalculated for each detector, where R_(b) is the baseline resistanceaveraged over approximately 20 s prior to vapor presentation, andΔR_(final) is the differential resistance change relative to R_(b). Thevalue of ΔR_(final) was evaluated over a period of approximately 20 s ata fixed time after initiating the vapor presentation. This time variedbetween the different types of experiments, either from 40 to 60 s, 200to 220 s or 240 to 260 s after the start of the vapor presentation. Forease of visualization on a common graph of the different absoluteresponses of the various detector/analyte combinations, the ΔR/R_(b)data in some figures have been normalized. In these figures, data werenormalized by the mean response value, (ΔR/R_(b))_(j), of the detectorin the physical position j for each set of identical exposures (i.e.,for exposures to a common analyte, or for exposures to a common analyteat a common flow rate, as specified). The value for j was chosen as theposition of the detector to first physically encounter the analyte.

[0152] The rms noise, N_(rms), of a detector was measured as thestandard deviation of the data points obtained from the multimeter inthe period immediately prior to each vapor presentation, divided by theaverage resistance value of the multimeter data points produced overthat same measurement period. The period used to measure this baselinenoise was equal to the time elapsed between determination of thebaseline resistance and the determination of the differential resistancechange upon analyte exposure. This ensured that the signals weremeasured in the same bandwidth as the noise. The multimeter was used todetermine both the signal and noise values for this calculation becauseit was desirable to measure the signal and noise of the detectors usingthe same instrumental apparatus (i.e., the N in S/N is N_(rms)). Thevalues of the S/N were calculated independently for each separatepresentation of analyte to each detector. For the multimeter measurementof the noise of the films of different sizes described above, the sameanalysis was used, except the noise was calculated over an interval ofonly 20 s, and 5 of these values, separated in time by 100 s, wereaveraged to generate N_(rms). Unlike the values for S_(n), which is ameasure of the noise power, these noise values, N_(rms), were firstsquared to yield N² _(rms) prior to plotting them against film volume.

Example 1

[0153] Spectral Noise Measurements

[0154] For measurements of the noise properties of the detector films,glass microscope slides were coated with a 50 nm thick layer of Au ontop of a 15-30 nm thick layer of Cr, in a pattern that producedrectangular gaps between two parallel metal contact regions. The ratioof the rectangular edge length to the gap length was 8:1, and thisaspect ratio was held constant as the area of the gap was varied. Afterfilm deposition, this procedure resulted in detector films of similarresistance values that had systematically varying film volumes. Carbonblack composite films containing either PEVA or PCL, and having areas of0.080, 0.30, 1.2, 1.3, 5.0, 33.0, and 132 mm², with resistance valuesranging from 70 to 160 kΩ, were then deposited onto these substrates.The resulting detector film thicknesses, which were between 180 and 300nm for the PEVA films and between 60 and 120 nm for the PCL films, weremeasured with a Sloan Dektak model 3030 profilometer.

[0155] Noise of the detector films was determined according to astandard method (Dziedzic, et al., J. Phys. D-Appl. Phys. 1998, 31,2091-2097; Deen, et al, J. Vac. Sci. Technol. B 1998, 16, 1881-1884).Briefly, the films were placed into a metal box and were biased with astack of batteries (18 volts total) that was connected in series to a 1MΩ resistance. The 1 MΩ low-noise resistance was formed from ten 100 kΩwire-wound resistors (Newark Electronics) that were soldered together inseries. The bias voltage across the detector film was ac coupled to anSR560 wide-band low noise voltage preamplifier (Stanford ResearchSystems), and the output of the preamplifier was sent to an SR785dynamic signal analyzer (Stanford Research Systems). Using an average of100 measurements, a power spectral density from 1 Hz to 800 Hz wascollected for each film. Data collection occurred over a period of inexcess of 100 s for each noise spectral power measurement. These spectrawere divided by the square of the bias voltage applied to thechemiresistor, V_(b) ², to yield the relative power spectral densityS_(n) for each detector film.

[0156] A control experiment was performed to evaluate whetherfilm-substrate contacts dominated the observed noise properties of thedetectors. Two composite films of approximately the same thickness, filmarea, and resistance were fabricated, with one film deposited in five0.38 mm gaps between ten parallel 5.0 mm wide Cr/Au electrical contactpads, and the other film deposited across only one 2.0 mm gap betweentwo parallel 5.0 mm wide Cr/Au contact pads. The additionalfilm/substrate contacts produced no change in the relative noise powerof the films, suggesting that the measured noise resulted primarily fromthe properties of the bulk detector film as opposed to the properties ofthe film electrode contacts. The properties of commercial, low noise,wire-wound resistors that had resistances similar to those of the carbonblack composite films were also measured. The much lower noise valuesobserved for these wire-wound resistors, which are known to exhibitlittle or no 1/f noise, confirmed that the Johnson noise of theresistors plus any additional amplifier noise of the experimental setupwas much lower than the 1/f noise observed for the carbon blackcomposite films. No correction for the amplifier noise was thereforeperformed in analysis of the noise data of the carbon black compositedetector films.

[0157]FIG. 7 displays the noise power spectral density, S_(n)(V_(b)),between 1 Hz and 800 Hz for a set of carbon black composite thin filmdetectors as a function of the area covered by the composite between theelectrical contact pads. Power spectral density of the noise,S_(n)(V_(b)), versus frequency, f, for seven poly (ethylene-co-vinylacetate), 25% acetate (PEVA)-carbon black composite detector films ofvarying area. The dimensions of the rectangularly shaped regions bridgedby polymeric composite between the electrical contact pads were (in mm):0.10×0.80, 0.20×1.60, 0.38×3.05, 0.40×3.20, 0.79×6.3, 2.03×16.3,4.06×32.5. The PEVA-carbon black composite films were ≈230 nm inthickness as determined by profilometry. The dashed line indicates a fitof one such plot to a function of the formS_(n)(V_(b))=1×10⁻⁸/f^(1.054). Also shown are data for a wire-wound, lownoise, 70 kΩ resistor. The electrode contact dimensions in theseexperiments were scaled such that the resistance (≈100 kΩ) wasapproximately constant as the film area was varied. Any variation in thenoise thus arose from the film area and not from a variation in responseof the preamplifier to different absolute input resistance values. Anadditional advantage of maintaining a constant aspect ratio for thedifferent volume films is to reduce the variation in the noise that hasbeen observed in some thick-film resistors of different aspect ratios.

[0158] The power spectral density of the carbon black-polymer thin filmcomposites was well-fit to a function of the form S_(n)(V_(b))∝1/f^(γ)with an exponent of γ=1.1. Some deviation from the 1/f behavior wasobserved at very low frequencies (<5 Hz), but this deviation may haveresulted from the mechanical contacts used to make connections to theAu/Cr/glass substrates. The noise power spectral density of thewire-wound resistor was much lower than the 1/f noise of any of thedetector films at the frequencies investigated in this study.

[0159]FIGS. 8A and 8B illustrates the value of the S_(n)*f product(crosses) for carbon black composite detectors fabricated from PEVA andPCL, respectively, as a function of the volume of the detector film. ThePEVA-carbon black composite films were ≈230 nm in thickness and thePCL-carbon black composites were ≈80 nm in thickness as determined byprofilometry. For these comparisons, the data were taken as the value ofS_(n) at 10 Hz to avoid the lower frequency contact noise. These valuesare directly comparable because they were taken at the same frequency,but the S_(n)*f product was displayed because it is essentiallyindependent of frequency for the 1/f region above about 5 Hz infrequency. Also shown are the square of the noise values, N² _(rms),(filled circles) derived from analysis of the standard deviation of thebaseline resistance values verses time as determined on these same filmsusing the multimeter. The detector films used in these experiments wereall approximately the same thickness, but the film volume data werecalculated using the actual thickness values determined fromprofilometry measurements of the thickness of each detector film.

[0160] The N² _(rms) and S_(n)*f values decreased approximately linearlywith the film volume, V, with a plot of S_(n)*f versus V forPEVA-containing carbon black composites having a slope of −0.95(R²=0.989) and a plot of N² _(rms) versus V having a slope of −0.91(R²=0.964). For the PCL-containing carbon black composite films, theslope of S_(n)*f versus V was −0.60 (R²=0.933) whereas the slope of N²_(rms) versus V was −0.58 (R²=0.833). It is difficult to perform aquantitative comparison between the S_(n)*f and N² _(rms) values, due tothe impedance mismatch between the input amplifier of the multimeter andthe resistive load of the detector, the variable bandwidth of themultimeter during various resistance readings, and other well-knownelectronic circuit considerations. However, the inverse dependence ofthe N² _(rms) value on the volume of the detector film is clearly seenin both sets of measurements. Deviations from a strictly lineardependence of the relative noise power on V with a slope of −1 have beenobserved previously for polymer film resistors, and have been explainedby factors arising from the film-electrode contacts, inhomogeneities infilm composition, and/or variability in film thickness over the measureddetector area. The deviations that observed here may also have resultedfrom properties related to the relatively thin nature of the films used.

Example 2

[0161] Determination of Polymer/Gas Partition Coefficients

[0162] Quartz crystal microbalance (QCM) measurements were performed onpure films of both PEVA and PCL at 294 K using 10 MHz resonant frequencyquartz crystals and a measurement apparatus as described in Severin, etal., Anal. Chem. 2000, 72, 2008-2015. Twenty vapor presentations, each120 s in duration and separated in time by 15 min, were performed ateach of 4 concentrations (P/P^(o)=0.010, 0.030, 0.050, 0.10) of n-hexaneand of methanol. The order of vapor presentation was randomized withrespect to analyte identity, analyte concentration, and repetition ofconditions. The frequency shifts of the polymer-coated QCM crystalsarising from deposition of the polymer film, Δf_(polymer), were recordedas the difference in the resonant frequency of the crystal before andafter deposition of the polymer film. The frequency change upon exposuretoe analyte vapor, Δf_(analyte), was calculated as the difference in theresonant frequency of the film-coated crystal during exposure to thespecific analyte vapor relative to the baseline resonant frequency ofthe film-coated crystal in background air. The baseline frequency wastaken as the mean frequency value obtained for the film-coated crystalduring a 30 s period immediately prior to exposure to the analyte, andthe frequency during exposure to analyte vapor was taken to be the meanfrequency value observed between 80 s and 110 s after the vapor exposurehad been initiated.

[0163] For a given volume of sampled analyte, the detector volume thatwill produce optimum signal/noise performance for a specificpolymer/analyte combination can be calculated from Equation 12 if thepolymer/gas partition coefficient is known. Accordingly, data for thepartition coefficients of hexane and methanol into PCL and PEVA weredetermined using QCM measurements. FIGS. 9A and 9B illustratedifferential frequency changes, −ΔAf_(analyte), of quartz crystalmicrobalances coated with PEVA (FIG. 9A) and PCL (FIG. 9B) polymer filmsduring exposure to hexane at P/P^(o)=0.010, 0.030, 0.050, and 0.10 (1.7,5.1, 8.5, 17 parts per thousand, ppth) and methanol at P/P_(o)=0.010,0.030, 0.050, and 0.10 (1.3, 4.1, 6.8, 14 ppth), where P is the partialpressure of analyte and P_(o) is the vapor pressure of the analyte at294 K. Each data point represents an average of 20 ΔR/R _(b) responses,and the error bars indicate plus and minus one standard deviation aroundthe mean. The frequency shifts corresponded to decreases in frequencyupon exposure to analyte. Lines were fitted through these points with aforced zero intercept. The slopes of these lines were a) hexane: 4.36(R²=0.9988); methanol: 0.910 (R²=0.9995); b) hexane: 0.612 (R²=0.9977);methanol: 0.930 (R²=0.9995). The frequency shifts due to coating thecrystal with the polymer were −6835 Hz for PEVA and −4355 Hz for PCL.

[0164] The frequency shifts of the polymer-coated QCM crystals arisingfrom deposition of the polymer film, Δf_(polymer) and from sorption ofthe analyte vapor, Δf_(analyte), were in total much less than 2% of theresonant frequency of the uncoated crystal. Under such conditions, ithas been reported that mechanical losses are minimal and that thefrequency shifts are predominantly due to changes in mass uptake (Lu,C., in Applications of Piezoelectric Quartz Crystal Microbalances; Lu,C. C., Ed., Elsevier, N.Y., 1984, Vol., 7, pp. 19-61), which can becalculated from the Sauerbrey equation (Lu, C., in Applications ofPiezoelectric Quartz Crystal Microbalances; Lu, C. C., Ed., Elsevier,N.Y., 1984, Vol., 7, pp. 19-61; Buttry, D. A., in ElectroanalyticalChemistry; A Series of Advances; Bard, A. J., Ed., Marcel Dekker, N.Y.,1991, Vol. 17, pp 1-85). Polymer/gas partition coefficients weretherefore calculated by fitting a line with a forced zero interceptthrough the Δf_(analyte) versus concentration data for eachpolymer/analyte combination. The slopes of these lines were −4.36(R²=0.9988) and −0.910 (R²=0.9995) for hexane and methanol,respectively, sorbing into PEVA, and were −0.612 (R²=0.9977) and −0.930(R²=0.9995) for hexane and methanol, respectively, sorbing into PCL. Theslopes of the resulting lines were converted into partition coefficientsusing:

K=(10⁶ ρRTm)/(M _(w) Δf_(polymer) P_(atm))  (13)

[0165] where R the ideal gas constant (L atm mol⁻¹ K⁻¹), ρ is thedensity (g ml⁻¹) of the polymer, T is the temperature (K), m is theslope of Δf_(analyte) versus concentration (Hz/parts per thousand inair), M_(w) is the molecular weight (g mol⁻¹) of the analyte,Δf_(polymer) (Hz) is the frequency shift corresponding to deposition ofthe polymer, and P_(atm) is the atmospheric pressure (atm). Thepartition coefficients for each analyte/polymer combination are shown inFIG. 10.

[0166] Partition coefficients for the lower vapor pressure analytes,dodecane and hexadecane, were difficult to measure because these verylow vapor pressure analytes adsorbed to the walls of the chamber andrequired long times as well as high analyte volumes to reach trueequilibrium conditions. Instead, the values for these analytes wereestimated by multiplying the measured polymer/gas partition coefficientsfor hexane by the ratio of the vapor pressures of dodecane andhexadecane relative to that of hexane (see Doleman, et al., Proc. Natl.Acad. Sci. U.S.A. 1998, 95, 5442-5447). This is a good approximationprovided that the activity coefficients do not vary significantly forsorption of these three alkanes into the polymers of interest. As shownin FIG. 10, the polymer/gas partition coefficients varied from measuredvalues of 10² for hexane and methanol to values of over 10⁷ estimatedfor the lowest vapor pressure analyte, hexadecane.

[0167] The wide difference in vapor pressures between the analytes ofconcern is expected to have a significant influence on the physicalarray design for optimization of the signal/noise ratio as given byEquation 9. In a chamber of headspace thickness of 1.0×10⁻² cm, with adetector film thickness of 1.0×10⁻⁴ cm, the optimum detector area for a1.0 cm³ volume of an analyte sample for which the analyte polymer/gaspartition coefficient is 1.0×10² is 1.0 cm². In contrast, for the samesampled volume, headspace thickness, and detector film thickness, adetector area of only 1.0×10⁻⁵ cm² produces maximum S/N performance foran analyte having a polymer/gas partition coefficient of 1.0×10⁷. Theimplications of this wide variation in polymer/gas partition coefficientfor optimizing the signal/noise performance of sorption-based vapordetectors are explored in detail below.

Example 3

[0168] Vapor Response of Linear Arrays of Chemically Equivalent,Spatially Nonequivalent Detectors

[0169] To investigate the spatiotemporal and geometric aspects of thechemiresistive vapor detectors, a linear array of detectors having adefined headspace and analyte flow configuration was constructed similarto the design illustrated in FIGS. 1A, 1B and 1C. A series of parallelCr/Au contacts was formed on each side of 75 mm×25 mm glass slides.These contact electrodes were 1.8 mm long and were separated by a gap of0.4 mm. Each pair of electrodes, which defined the contacts for anindividual detector, was spaced 5 mm apart, permitting formation of 15individual detectors on each side of the glass slide. The areasurrounding the electrodes was coated with a thin layer of Teflon.

[0170] Both sides of the substrate were masked, with the exception of a5 mm by 75 mm rectangular region on each side of the substrate that wascentered on the row of electrical contacts used to form the detectors.Through this mask, carbon black-PEVA composites were sprayed onto oneside of the glass microscope slide and carbon black-PCL composites weresprayed onto the other side of the glass slide. After spraying, thecarbon black-polymer films covered the entire length of these substrates(Scheme II). Two such substrates were prepared. On the first substrate,the resulting detectors had resistance values that ranged from 60 to 160kΩ on the side sprayed with a PCL-carbon black composite and from 140 to180 kΩ on the side sprayed with a PEVA-carbon black composite. Theranges on the second substrate were 70 to 110 kΩ on the side sprayedwith the PCL-carbon black composite and 170 to 260 kΩ on the sidesprayed with a PEVA-carbon black composite.

[0171] A low volume vapor sample chamber was custom fabricated for thevapor response experiments. The detector substrate was placed betweentwo pieces of A1, each of which had a recess 3.5 mm wide and 400 μm indepth machined along its length. Prior to assembly, a thin piece ofTeflon tape was smoothed over the surface of the A1 pieces and into thechannel, effectively lining the top and the sides of the channel with an≈60 μm thick layer of Teflon. This Teflon prevented contact between theanalyte and the A1 and also formed an airtight gasket between each A1piece and the substrate. Assembly of the A1 pieces and the substratecreated one shallow channel above the substrate and one shallow channelbelow the substrate, with each channel being 340 μm deep (400 μm channeldepth minus 60 μm thickness of Teflon insulation) and 3.4 mm wide (3.5mm machined width minus 2×0.06 mm thickness of Teflon insulation). Eachchannel spanned the entire length of the row of 15 detectors on itscorresponding side of the substrate. The 3.4 mm width of the channelbounded the gas flow into a region that was less than the width of thedetector film that had been sprayed onto the substrate. Hence, for theentire length of the channel, the detector film completely coated thesubstrate in the region adjacent to the channel.

[0172] The responses of arrays of carbon black-polymer composite vapordetectors were investigated as a function of position relative to thelocation of analyte flow injected into the detection chamber. Thepattern of the contacts beneath the film of carbon black/polymercomposite in the linear sensor array produced an array of chemiresistivedetectors that were arranged in a linear geometry, parallel to theanalyte flow path, and which were spaced at 5 mm intervals downstreamfrom the location of flow injection. The headspace volume was defined bythe 3.4 mm width, 340 μm depth, and 75 mm total length of this channelover the detector film. The area of the carbon black-polymer compositefilm spanned the entire length of the substrate and was sufficientlywide to ensure that the entire region of the substrate in contact withthis vapor channel was coated with the detector film. Hence, in manyrespects this experimental apparatus is analogous to probing thespatiotemporal distribution of analyte in the sorbent phase afterinjection of a sample onto a gas chromatography column or toascertaining spectroscopically the position of analyte in a thin layerchromatography experiment as a function of time.

[0173]FIG. 11 displays data collected for the array exposed in thisconfiguration at a fixed, low carrier gas flow rate of three analytes ofdiffering vapor pressure (hexane, dodecane, and tridecane, vaporpressure of 3.9×10⁻² torr at 294 K, each at a constant activity ofP/P^(o)=0.10 and at a volumetric flow rate of 6 ml min⁻¹), to a seriesof PEVA-carbon black composites. The data are the relative differentialresistance values measured in a 20 s period after 240 s of continuousexposure to the various analytes of interest. The analyte exposures usedto produce these data were randomized with respect to analyte identityand with respect to the 5 replicate exposures of each analyte at theconcentration of interest. For ease of visualization on a common graphof the different absolute responses of the various detector/analytecombinations, the data in this figure have been normalized relative tothe mean response of the first detector that physically encountered theanalyte. The solid lines indicate responses when the analyte flowed inthe direction from the leftmost detector (corresponding to the detectorwith the lowest numbered position) to rightmost detector. These data(and associated standard deviations) were normalized to the meanresponse value of the detector in position 1 in the array (j=1) for the5 exposures to the analyte of interest. The normalization constants(values by which the data were multiplied for display on the plot) are:10.8, 16.7, and 32.1, for hexane, dodecane, and tridecane, respectively.The dashed lines indicate responses recorded when the same row ofdetectors was exposed to vapor flowing in the opposite direction throughthe detector chamber; consequently, these data (and associated standarddeviations) were normalized to the mean response value of the detectorin position 15 in the array (j=15) to the 5 exposures of the analyte ofinterest. Normalization constants for these data are: 10.4, 15.3, and30.2, for hexane, dodecane, and tridecane, respectively.

[0174] For high vapor pressure analytes, the detectors all producednominally identical responses to the analyte after this exposure period.For example, the standard deviation of the mean response to hexane atP/P^(o)=0.10 for the 15 nominally identical detectors was less than 5%of the mean ΔR/R_(b) response value for this detector/analytecombination. This degree of reproducibility is consistent with priorreports that have evaluated the reproducibility of the response ofcarbon black/polymer composite detectors (Lonergan, et al., Chem. Mat.1996, 8, 2298-2312).

[0175] In contrast, for exposures to low vapor pressure analytes such astridecane, the ΔR/R_(b) values observed from the detectors to firstencounter the vapor stream were much higher than ΔR/R_(b) valuesobserved for detectors located at positions remote from the injectionlocation. The position-related variation in ΔR/R_(b) in response to thelow vapor pressure analytes was clearly much greater than the standarddeviation of the ΔR/R_(b) value observed for replicate exposures to anyof the analytes investigated. The trend was systematic in that thedetectors closest to the analyte injection position displayed thehighest ΔR/R_(b) values, the response decreased monotonically withposition from the location of analyte injection, and the magnitude ofthe effect increased as the vapor pressure of the analyte decreased.Furthermore, for the low vapor pressure analytes the change in meanresponse versus detector position far exceeded the standard deviation ofthe mean responses observed for these same detectors when exposed, inthe identical apparatus, to analytes having high vapor pressures.

[0176] To conclusively prove that the effect was associated with thegeometry of the flow system relative to the position of the detectors inthe chamber, and not with any physicochemical inequivalence in thedetectors themselves, the position of analyte injection was changed suchthat the flow proceeded in the opposite direction through the chamber,with analyte first encountering detector number 15 and finallyencountering detector number 1 in FIG. 1A. The same analytes were usedand the order of presentation was again randomized with respect tosolvent identity and with respect to the five replicate exposures toeach analyte; however, the exposure order was the same as that used whenthe flow proceeded from low to high detector number. As shown in FIG.11, the detectors again provided essentially equivalent responses whenexposed to high vapor pressure analytes at a volumetric flow rate of 6ml min⁻¹. For low vapor pressure analytes, the highest ΔR/R_(b) valueswere again observed from the detectors that first physically encounteredthe vapor stream.

[0177]FIGS. 12A and 12B display similar data, collected on a differentsubstrate, as a function of analyte flow velocity. Data presented arefor two analytes, one having a high vapor pressure (hexane) and theother having a low vapor pressure (dodecane), both exposed to eitherPEVA-carbon black (FIG. 12A) or to PCL-carbon black (FIG. 12B) compositedetector films. For each flow rate, hexane and dodecane were alternatelypresented to the detectors. This procedure was repeated for each of 5flow rates, proceeding sequentially from the lowest volumetric flow rateto the highest volumetric flow rate. This 10 exposure protocol was thenrepeated in its entirety 4 times, producing 50 total exposures ofanalyte to the detectors.

[0178] For high vapor pressure analytes (i.e., analytes with relativelysmall polymer/gas partition coefficients), all of the detectorsexhibited essentially the same ΔR/R_(b) response values in the 20 speriod after 240 s of analyte exposure at all tested flow rates,regardless of the position of the detector relative to the point ofanalyte injection. This is expected because the analyte sorption processdetermines the steady-state value of ΔR/R_(b), and because all of thedetectors experienced essentially identical concentrations of analyteunder such conditions.

[0179] Low vapor pressure analytes (i.e. analytes with large polymer/gaspartition coefficients), however, produced different behavior. At highflow rates, all detectors produced essentially identical ΔR/R_(b)signals in the 20 s period after 240 s of analyte exposure, furtherconfirming that the concentration of the analyte in proximity to eachdetector was similar and that the detectors themselves were very similarin response properties. However, at lower flow rates, lower ΔR/R_(b)values were observed in the 20 s period after 240 s of analyte exposurefor the detectors to last encounter the vapor stream. To confirm thatthis effect was due to the physical location of the detector relative tothe position of analyte flow injection, the direction of analyte flow inthe chamber was again reversed and data were recollected for the entiresequence of analyte exposures. The lowest ΔR/R_(b) responses were againobserved for detectors that were located farthest from the position ofanalyte injection.

[0180] The concentration of the low vapor pressure analyte stream isdepleted by sorption into the first region of polymer composite filmthat it encounters, and the analyte concentration in the boundary layerthat is exposed to the film is decreased further as the gas flowprogresses along the length of the polymer composite. For analytes oflow vapor pressure, all detectors produced essentially identicalresponses at high flow rates, whereas at sufficiently low flow ratesdifferent responses were observed for detectors located in differentpositions relative to the position of analyte injection into thechamber. In this transitional region of behavior, analysis of therelative signal strengths of the detectors in the array can provideinformation on the partition coefficient of the analyte into the polymerfilm of interest. FIG. 11 shows this effect for hexane, dodecane, andtridecane.

[0181] The effect of sorption of low vapor pressure analytes into thecomposite vapor detector films is also evident in the temporal responseof the detectors. FIG. 13 shows resistance versus time data for exposureof a PEVA-carbon black composite to hexane (at P/P^(o)=0.10) followedimmediately by exposure to a mixture of hexane and dodecane (each atP/P^(o)=0.10). These data were obtained at a relatively low carrier flowvelocity (6 ml min⁻¹) on a PEVA-carbon black detector located atposition 7 in FIG. 1A. Under these conditions, the different analytescan be distinguished based on their characteristic temporal responses onthis detector that arise from the interactions with the analyte flow inthe detector chamber.

Example 4

[0182] Vapor Response of Stacked Arrays of Chemically Equivalent,Spatially Nonequivalent Detectors

[0183] The results obtained in Example 3 indicate that the noisedecreases approximately as the square root of the detector area. Thus,for sufficient headspace volumes and quantities of sampled analyte sothat the concentration of analyte sorbed into the polymer film remainsconstant as the detector area increases (as given by K=C_(p)/C_(v)^(eq)), an increased detector area will produce no change in themagnitude of the steady-state signal, a reduced value of the noise, andhence an increase in S/N ratio. However, for finite duration pulses oflow vapor pressure compounds injected at low flow rates onto polymerfilms that have large polymer/gas partition coefficients, analytesorption will only effectively occur onto the subset of detectors thatare encountered initially by the analyte flow. In this situation,increasing the detector area decreases the S/N ratio and additionallymasks the spatiotemporal dependence of analyte sorption that can be usedto discriminate between analytes of differing polymer/gas partitioncoefficients (FIGS. 11-13). In this section, we describe the results ofexperiments designed to exploit both aspects of these properties ofdetector/analyte/flow interactions.

[0184] To investigate this trade-off between detector S/N and detectorarea, stacked sensor arrays were constructed according to FIGS. 5A and5B, using rectangular 20 mm by 23 mm substrates that were fabricated bya commercial vendor (Power Circuits, Santa Ana, Calif.) using standardprinted circuit board technology. Each of these substrates hadelectrical contacts deposited in a pattern that created a total of sixdetectors. Three detectors were located on the face of the substrate andthree on the edge of the substrate. The three leading edge detectorswere formed on the 840 μm thick edge of the substrate between parallelcontacts that were located on each face of the circuit board. Thesedetectors were located in positions 1 e, 2 e and 3 e in FIG. 5B. The 20mm by 23 mm faces of the circuit board supported the three largerdetectors, each of which had dimensions of 2.0 mm by 15 mm (positions 1f, 2 f, and 3 f in FIG. 5B). The electrodes that formed face detectorsin the same location on the top and bottom of each substrate were wiredtogether in parallel (i.e. the leads to detector if on the top face wereconnected in parallel to the leads that addressed detector If on thebottom face of the substrate). On each substrate this arrangementtherefore produced three face detectors, each having a total film areaof 60 mm² (2×2.0 mm×15 mm).

[0185] Six total substrates of this type were prepared. Three of thesesubstrates were prepared by spraying PEVA-carbon black films onto theedge and face detectors of the substrates, and three by sprayingPCL-carbon black films onto the edge and face detectors of thesubstrates. To prevent current leakage between adjacent detectors, thefilms of the all individual detectors were isolated from each other bymasking during spraying to produce a narrow (1 mm wide) gap in thedetector film between adjacent detectors. Each of the six substrates wassprayed from an independently prepared suspension of carbon black andpolymer, but both faces and the leading edge of a given substrate weresprayed from the same suspension. The two faces of a substrate werecoated with a film of approximately the same resistance, to create filmsof similar thickness on each side of a given substrate.

[0186] One substrate sprayed with a PEVA-carbon black composite and onesprayed with a PCL-carbon black composite were then assembled into astack that also contained 760 μm thick A1 plates and 105 μm thick Teflonspacers. This assembly created a set of small channels, each ofdimensions 0.105 mm×12 mm×23 mm, that permitted vapor to be drawn overeach set of face detectors. The Teflon spacers served as the side wallsfor each channel. The assembled stack was 4.59 mm high (2×0.840mm+3×0.760 mm+6×0.105 mm). Three separate stack assemblies of this typewere built.

[0187] The stack assemblies were fitted into an A1 chamber that had anopen front and a tube connector on the back (away from the leading edgedetectors). This tube connector was piped to a vacuum pump through acombination airflow meter and regulator (Cole Parmer). Each of the threestack assemblies used in this experiment contained six total channelsformed collectively between the two substrates, the three A1 plates, andthe two walls of the chamber. Hence the volumetric flow of sampled gasthrough each individual channel was ⅙ of the volumetric flow of samplegas through the entire stack assembly.

[0188] These stacked detector arrays were exposed to various analytes ofinterest. In this configuration, with a detector film deposited on theedge of the substrate, and two other detector films of nominallyidentical composition deposited onto the two faces of the substrate, theface detector serves in essence as one large collection of detectorsarranged linearly as in Example 3, thereby inherently averaging theresponses, and providing reduced noise, for analytes with smallpolymer/gas partition coefficients. In contrast, the edge detector has asmall area so that it can provide enhanced S/N performance for analyteswith large polymer/gas partition coefficients. Two such substrates werethen stacked such that the leading edge of each detector firstencountered the analyte flow, with a component of the flow subsequentlybeing directed along the faces of the substrate. One substrate had onepolymer type forming its detectors and the other substrate had aseparate, different carbon black/polymer composite material forming allof its detectors. The gaps between the substrates and the adjacent A1plates were sufficiently thin to insure that the flow would proceed inthe desired direction. The entire experimental procedure and datacollection were fully repeated 3 independent times, each time with 2independently prepared substrates that were assembled into the stackedconfiguration of FIGS. 5A and 5B.

[0189] The ΔR/R_(b) responses, N_(rms) values, and S/N values (FIG. 10)for each stack assembly are averages over the three detectors of thesame geometry (face or edge) on a single substrate for 10 exposures to agiven analyte. In FIG. 10, the results of the experiments on the threeindependently prepared stack devices are displayed separately. Theaverage responses to high vapor pressure analytes (hexane and methanol)on the face detectors were between 75 and 100% of the magnitude of theresponses on the edge detectors, while the lowest vapor pressureanalyte, hexadecane, produced responses on the face detector that wereall less than 15% of the values observed on the edge detectors (FIG.10). This difference was much greater than the standard deviation of theresponses of either all of the face detectors or all of the edgedetectors on given substrate to an exposure to the analyte of interest.

[0190] The detector films on the leading edge of the substrate had{fraction (1/24)} the area of the films on the face of the detectors,and therefore exhibited higher noise levels than the detectors on theface of the substrate. Noise values, N_(rms), in the dc resistancereadings measured using the multimeter were on average eight timeshigher for the PCL edge detectors than for the PCL face detectors, andwere on average four times higher for the PEVA edge detectors than thePEVA face detectors (FIG. 10). The high vapor pressure analytes producedsimilar ΔR/R_(b) values on both detector types when exposed to methanolor hexane, hence the face detectors exhibited S/N ratios that reflectedthe decrease in noise produced by large volume detector films. For 200 sexposures to hexane, S/N values were ≈6 times higher for PCL facedetectors and were ≈4 times higher for PEVA face detectors than for thecorresponding edge detectors. In contrast, for 200 s exposures tohexadecane, the analyte with the lowest vapor pressure, the S/N valueswere about twice as high on the leading edge detectors as on the facedetectors. Thus, the different geometric form factors and interactionswith the analyte flow streamlines produced different performancecharacteristics from a S/N viewpoint for these different types ofdetectors.

[0191] The temporal evolution of the detector response properties canalso be used to differentiate between analytes. As shown in FIGS. 14Aand 14B, the responses of the face and edge detectors to hexane weresimilar after 40 s of vapor presentation, and remained similar after 200s. These hexane responses are similar in magnitude to the signals fordodecane after 200 s (FIG. 14B), and the two analytes could not easilybe distinguished based on these data alone. However, the responses forthese two analytes are clearly separable at 40 S (FIG. 14A), when thehexane has fully equilibrated with the given polymer film area but thedodecane is still being depleted from the analyte sample due to its veryhigh polymer/gas partition coefficient. The separation of these analytesas a function of time therefore demonstrates an increase in theresolving power attainable through the use of such spatiotemporalresponse information in conjunction with a spatially ordered array ofvapor detectors.

Example 5

[0192] Response at Constant Flow Rate of a Detector Array in thePresence of Volatile Organic Compounds and Water

[0193] To further investigate the effects of interfering analytes on thedetection of a target analyte, additional stacked sensor arrays wereprepared. Nine detector composite types were used, each fabricated froma different insulating polymeric phase. The materials used to form theseinsulating phases for the detectors of the corresponding number areshown in Table 3. TABLE 3 Detector Material: Detector Material: 1. PEVA(25% VA) 6. PMMA + diethylene glycol 2. Polyethylene oxide dibenzoate50% (wt/wt) 3. Polycaprolactone 7. PEVA (45% VA) 4. Poly(vinyl stearate)8. Styrene/isoprene 5. Polyvinylacetate + diethylene 9.polymethyloctadecyl siloxane glycol dibenzoate 50% (wt/wt)

[0194] The composites used in this experiment were sprayed onto threecircuit board substrates as illustrated in FIG. 15. Each substrate hadelectrical contacts deposited in a pattern that created a total of sixdetectors. Three detectors were located on each face (top and bottom) ofthe substrate and three detectors (of the same detector material) werelocated on the edge of the substrate. The three leading edge detectorswere formed on the 840 μm thick edge of the substrate between parallelcontacts that were located on each face of the circuit board. Thesedetectors were located in positions 1, 2 and 3 of FIG. 15. The 20 mm by23 mm faces of the circuit board supported the three larger detectors,each of which had dimensions of 2.0 mm by 15 mm. The electrodes thatformed face detectors in the same location on the top and bottom of eachsubstrate were wired together in parallel (i.e. the leads to facedetector 1 on the top face were connected in parallel to the leads thataddressed face detector 1 on the bottom face of the substrate). On eachsubstrate this arrangement therefore produced three face detectors, eachhaving a total film area of 60 mm² (2×2.0 mm×15 mm). Three of thesesubstrates were stacked so that their leading edges were normal to theflow, and the flow through the gaps was controlled with a pump at 100 mlmin⁻¹; consequently, the total flow of the diluted vapor stream betweeneach chip was much lower than that directed at the edge detectors.

[0195] Saturated DNT vapor at 21° C. was obtained from a glass tubeapproximately one meter in length that held ≈180 g of loosely packed,granulated DNT. The air flow through this tube was 200 ml min⁻¹, withthe background gas being oil-free laboratory air (1.10±0.15 parts perthousand (ppth) of water vapor). An additional gas stream passed througha bubbler that contained either acetone or water. Two in-line union-T'swere used to mix the DNT vapor stream, the stream that contained eitherof the “interfering” vapors, and a background laboratory air gas stream.Flows were controlled with Teflon solenoid valves and mass flowcontrollers, in a computer-controlled system as described in Severin, etal., Anal. Chem. 2000, 72, 658-668. A short Teflon tube was connected tothe output of the union to direct the gas toward the bank of detectors.The total flow rate of the gas directed at the detectors was heldconstant at 2 L min⁻¹ during all parts of the experiment. The DNTconcentration after dilution was 10% of its vapor pressure. At thisdilution, the upper limit of the DNT concentration is 14 parts perbillion (ppb) because the vapor pressure of DNT at room temperature isapproximately 140 ppb. When present in the vapor stream, theconcentration of the acetone was 12.9 parts per thousand (ppth).Although the background air stream always contained some water vapor,the concentration was roughly doubled to ≈2.3 ppth during exposures thatcontained water as an “interfering” vapor. During exposures of thedetector array, the vapor stream contained either pure DNT, water, oracetone; mixtures of DNT and water vapor; or mixtures of DNT and acetonevapor. Analyte exposures were 10 min in duration, and were separated intime by a 40 min exposure to the background air stream.

[0196] The average ΔR/R response (computed as the baseline normalizeddifferential resistance change of the detectors for 10 presentations ofeach vapor or mixture after 10 minute exposures to ppb levels of DNT inthe presence of ppth levels of two potentially interfering compounds) ofthe array of 18 detectors to DNT and to mixtures of DNT that containedhigh concentrations of either acetone or water vapor is shown in FIG.16. For pure analytes, vapors with small polymer/gas partitioncoefficients (generally analytes with high vapor pressures) producedsimilar magnitude signals on the leading edge and the corresponding facedetector having the same composite material. In contrast, virtually allof the DNT (having a low vapor pressure and therefore a high polymer/gaspartition coefficient in general) was trapped on the leading edgedetectors and produced essentially no response on the face detectors.For mixtures that contained both DNT and high vapor pressure analytes,subtraction of the face detector response from the edge detectorresponse yielded the response of only the low vapor pressure (highpolymer/gas partition coefficient) component of the vapor mixture.Because the responses of carbon black-polymer composite films are linearwith respect to concentration and additive with respect to components ofbinary mixtures (Severin, et al., Anal. Chem. 2000, 72, 658-668),subtraction techniques of this type can be applied without priorknowledge of the concentration or response pattern of the interferingvapor or knowledge of the effectiveness of the mass transport of the DNTvapor to the detector film.

[0197] The responses to the high vapor pressure analyte on the largeface detectors were first corrected by the slight variation in therelative sensitivity to both types of individual detectors (face andedge) and then subtracted to yield the response pattern of the pure DNT.This variation in sensitivity is expected to be independent of theconcentration of the interfering analyte, permitting this correction tomade against unknown concentrations of any contaminant analyteexhibiting small polymer/gas partition coefficients. The normalizedarray fingerprint patterns of pure DNT, and DNT in the presence of largeconcentrations of acetone or water are shown in FIG. 17. As FIG. 17shows, the extrapolated response pattern of the detectors is similar tothat of pure DNT even though the DNT was in the presence of much higherconcentrations of acetone or water. Although the pre-equilibrium (timedependent) response pattern of the detectors to DNT or to any otheranalyte with a very high partition coefficient is expected to dependmore closely on the film thickness of the individual detectors than onthe specific interactions between the analyte and polymers of theindividual detectors, the response pattern of the detectors to DNT isexpected to be characteristic and is therefore useful in elucidating theexistence of such a compound in the presence of high concentrations ofinterfering low partition coefficient compounds. Because responses ofcarbon black-polymer composite are additive in nature, subtractiontechniques of this type could potentially remove an unlimited number ofunknown interfering VOC's and water present simultaneously from thearray pattern of DNT, provided that the relative sensitivity to theseanalytes on face and edge detectors is similar, as expected, for a givenpolymer composite. This hardware-based preprocessing capabilitycircumvents many of the limitations of software-based pattern matchingalgorithms based on the face detector response alone, which wouldrequire prior knowledge of the array response to the specificinterfering analyte and would encounter difficulties with the occurrenceof high numbers of vapors simultaneously present in the vaporsurrounding the DNT target.

[0198] While the invention has been described in detail with referenceto certain embodiments thereof, it will be understood that modificationsand variations are within the spirit and scope of that which isdescribed and claimed.

What is claimed is:
 1. A flow-through fluid analysis system fordetecting an analyte in a fluid flow, comprising: a sensor array havinga first face and a second face, the sensor array including one or morefirst sensors and one or more fluid channels extending from the firstface to the second face, at least one of the first sensors being locatedat a first position in the sensor array in contact with the first faceof the sensor array, the one or more first sensors being configured togenerate a response upon exposure of the sensor array to at least oneanalyte in a fluid flow; a fluid flow system for introducing a fluidflow containing an analyte to the sensor array, such that uponintroduction of a fluid flow to the sensor array a pressure differentialis created between the first and second faces of the sensor array; and aprocessor configured to receive the response generated by the one ormore first sensors and to process the response to detect at least oneanalyte in a fluid flow.
 2. The system of claim 1, wherein: the sensorarray includes a substrate having a first surface and a second surface;and the fluid channels extend from the first surface to the secondsurface.
 3. The system of claim 2, wherein: the fluid channels include aplurality of pores in a microporous substrate material.
 4. The system ofclaim 2, wherein: the fluid channels include a plurality of holesintroduced into an impermeable substrate material.
 5. The system ofclaim 4, wherein: the fluid flow system includes a predeterminedsampling volume, the sensor array is located within the sampling volume,and the first sensor has a sensor volume, the sensor volume beingsubstantially optimized to cause the first sensor to generate a responsehaving a maximum signal to noise ratio for at least one target analyte.6. The system of claim 5, wherein: the sensor volume is substantiallyoptimized as a function of a partition coefficient K of at least onetarget analyte.
 7. The system of claim 6, wherein: the predeterminedsampling volume includes a headspace proximate to the first sensor, theheadspace having a headspace volume V_(l); and the sensor volume V_(p)is substantially optimized based on the function V_(p)=V_(l)/K.
 8. Thesystem of claim 1, wherein: the one or more first sensors include avapor sensor for detecting an analyte in a gas.
 9. The system of claim8, wherein: the one or more first sensors include a plurality of vaporsensors for detecting an analyte in a gas.
 10. The system of claim 1,wherein: the one or more first sensors include a liquid sensor fordetecting an analyte in a liquid.
 11. The system of claim 10, wherein:the one or more first sensors include a plurality of liquid sensors fordetecting an analyte in a liquid.
 12. The system of claim 1, wherein:the sensor array includes at least one second sensor located at a secondposition in the sensor array, the second position being different fromthe first position relative to the fluid flow, the first and secondsensors each generating a response upon exposure of the sensor array toat least one analyte in a fluid flow, such that the responses generatedupon exposure of the sensor array to at least one analyte in a fluidflow include a spatio-temporal difference between the responses for thefirst and second sensors.
 13. The system of claim 12, wherein: theprocessor is configured to resolve a plurality of analytes in a fluidflow upon exposure of the sensor array to a fluid flow containing theplurality of analytes.
 14. The system of claim 1, wherein: the sensorarray includes a plurality of second sensors, each of the first sensorand a plurality of the second sensors being located at a differentposition in the sensor array relative to the fluid flow, the first andsecond sensors each generating a response upon exposure of the sensorarray to at least one analyte in a fluid flow, such that the responsesgenerated upon exposure of the sensor array to at least one analyte in afluid flow include a spatio-temporal difference between the responsesfor the first and second sensors.
 15. The system of claim 1, wherein:the sensor array includes a first substrate forming a plate having alength, a width, and a depth, such that the length and the width incombination define a pair of substrate faces and the width and the depthin combination define a pair of substrate edges, the first substratebeing oriented in the sampling volume such that the substrate facesextend in a direction parallel to a direction of the fluid flow and thesubstrate edges are situated normal to the fluid flow; and the one ormore first sensor are located on one of the pair of substrate edges. 16.The system of claim 15, wherein: the sensor array includes one or moresecond sensors located on one of the pair of substrate faces.
 17. Thesystem of claim 14, wherein: the processor is configured to resolve aplurality of analytes in a fluid flow upon exposure of the sensor arrayto a fluid flow containing the plurality of analytes.
 18. The system ofclaim 15, wherein: the sensor array includes a plurality of secondsensors located at different positions along one of the pair ofsubstrate faces, such that the responses generated upon exposure of thesensor array to at least one analyte in a fluid flow include aspatio-temporal difference between responses generated by each of thefirst and the plurality of the second sensors.
 19. The system of claim16, wherein: the sensor array includes a plurality of substrates, eachsubstrate forming a plate having a length, a width, and a depth, suchthat for each of the substrates the length and the width in combinationdefine a pair of substrate faces and the width and the depth incombination define a pair of substrate edges, the substrates beingoriented in the sampling volume such that the substrate faces extend ina direction parallel to a direction of the fluid flow and the substrateedges are situated normal to the fluid flow; and for each of theplurality of substrates, the sensor array includes one or more firstsensors located on one of the pair of substrate edges and one or moresecond sensors located on at least one of the pair of substrate faces.20. The system of claim 16, wherein: at least one of the first sensor orthe second sensors has a sensor volume, the sensor volume beingsubstantially optimized to achieve a maximum signal to noise ratio forat least one target analyte.
 21. The system of claim 20, wherein: thesensor volume is substantially optimized as a function of a partitioncoefficient K of at least one target analyte.
 22. The system of claim21, wherein: the predetermined sampling volume includes a headspaceproximate to the first sensor, the headspace having a headspace volumeV_(l); and the sensor volume V_(p) is substantially optimized based onthe function V_(p)=V_(l)/K.
 23. The system of claim 15, wherein: the oneor more first sensors include a vapor sensor for detecting an analyte ina gas.
 24. The system of claim 23, wherein: the one or more firstsensors include a plurality of vapor sensors for detecting an analyte ina gas.
 25. The system of claim 15, wherein: the one or more firstsensors include a liquid sensor for detecting an analyte in a liquid.26. The system of claim 25, wherein: the one or more first sensorsinclude a plurality of liquid sensors for detecting an analyte in aliquid.
 27. A method of detecting an analyte in a fluid flow,comprising: providing a sensor array having a first face and a secondface, the sensor array including one or more first sensors and one ormore fluid channels extending from the first face to the second face, atleast one of the first sensors being located at a first position in thesensor array in contact with the first face of the sensor array, the oneor more first sensors being configured to generate a response uponexposure of the sensor array to at least one analyte in a fluid flow;exposing the sensor array to a fluid flow including an analyte underconditions sufficient to create a pressure differential between thefirst and second faces of the sensor array; measuring a response for theone or more first sensors; and detecting the presence of the analyte inthe fluid based on the measured response.
 28. The method of claim 27,wherein: the sensor array includes a substrate having a first surfaceand a second surface; and the fluid channels extend from the firstsurface to the second surface.
 29. The method of claim 28, wherein: thefluid channels include a plurality of pores in a microporous substratematerial.
 30. The method of claim 28, wherein: the fluid channelsinclude a plurality of holes introduced into an impermeable substratematerial.
 31. The method of claim 30, wherein: the first sensor has asensor volume, the sensor volume being substantially optimized to causethe first sensor to generate a response having a maximum signal to noiseratio for at least one target analyte.
 32. The method of claim 31,wherein: the sensor volume is substantially optimized as a function of apartition coefficient K of at least one target analyte.
 33. The methodof claim 32, wherein: the predetermined sampling volume includes aheadspace proximate to the first sensor, the headspace having aheadspace volume V_(l); and the sensor volume V_(p) is substantiallyoptimized based on the function V_(p)=V_(l)/K.
 34. The method of claim27, wherein: the one or more first sensors include a vapor sensor fordetecting an analyte in a gas.
 35. The method of claim 34, wherein: theone or more first sensors include a plurality of vapor sensors fordetecting an analyte in a gas.
 36. The method of claim 27, wherein: theone or more first sensors include a liquid sensor for detecting ananalyte in a liquid.
 37. The method of claim 36, wherein: the one ormore first sensors include a plurality of liquid sensors for detectingan analyte in a liquid.
 38. The method of claim 27, wherein: the sensorarray includes at least one second sensor located at a second positionin the sensor array, the second position being different from the firstposition relative to the fluid flow, the first and second sensors eachgenerating a response upon exposure of the sensor array to at least oneanalyte in a fluid flow, such that the responses generated upon exposureof the sensor array to at least one analyte in a fluid flow include aspatio-temporal difference between the responses for the first andsecond sensors.
 39. The method of claim 38, wherein: detecting thepresence of the analyte in the fluid includes resolving a plurality ofanalytes in the fluid based on the measured response.
 40. The method ofclaim 27, wherein: the sensor array includes a plurality of secondsensors, each of the first sensor and a plurality of the second sensorsbeing located at a different position in the sensor array relative tothe fluid flow, the first and second sensors each generating a responseupon exposure of the sensor array to at least one analyte in a fluidflow, such that the responses generated upon exposure of the sensorarray to at least one analyte in a fluid flow include a spatio-temporaldifference between the responses for the first and second sensors. 41.The method of claim 27, wherein: the sensor array includes a firstsubstrate forming a plate having a length, a width, and a depth, suchthat the length and the width in combination define a pair of substratefaces and the width and the depth in combination define a pair ofsubstrate edges, the first substrate being oriented in the samplingvolume such that the substrate faces extend in a direction parallel to adirection of the fluid flow and the substrate edges are situated normalto the fluid flow; and the one or more first sensor are located on oneof the pair of substrate edges.
 42. The method of claim 41, wherein: thesensor array includes one or more second sensors located on one of thepair of substrate faces.
 43. The method of claim 40, wherein: detectingthe presence of the analyte in the fluid includes resolving a pluralityof analytes in the fluid based on the measured response.
 44. The methodof claim 41, wherein: the sensor array includes a plurality of secondsensors located at different positions along one of the pair ofsubstrate faces, such that the responses generated upon exposure of thesensor array to at least one analyte in a fluid flow include aspatio-temporal difference between responses generated by each of thefirst and the plurality of the second sensors.
 45. The method of claim42, wherein: the sensor array includes a plurality of substrates, eachsubstrate forming a plate having a length, a width, and a depth, suchthat for each of the substrates the length and the width in combinationdefine a pair of substrate faces and the width and the depth incombination define a pair of substrate edges, the substrates beingoriented in the sampling volume such that the substrate faces extend ina direction parallel to a direction of the fluid flow and the substrateedges are situated normal to the fluid flow; and for each of theplurality of substrates, the sensor array includes one or more firstsensors located on one of the pair of substrate edges and one or moresecond sensors located on at least one of the pair of substrate faces.46. The method of claim 42, wherein: at least one of the first sensor orthe second sensors has a sensor volume, the sensor volume beingoptimized to achieve a maximum signal to noise ratio for at least onetarget analyte.
 47. The method of claim 46, wherein: the sensor volumeis optimized as a function of a partition coefficient K of at least onetarget analyte.
 48. The method of claim 47, wherein: the predeterminedsampling volume includes a headspace proximate to the first sensor, theheadspace having a headspace volume V_(l); and the sensor volume V_(p)is optimized based on the function V_(p)=V_(l)/K.
 49. The method ofclaim 41, wherein: the one or more first sensors include a vapor sensorfor detecting an analyte in a gas.
 50. The method of claim 49, wherein:the one or more first sensors include a plurality of vapor sensors fordetecting an analyte in a gas.
 51. The method of claim 41, wherein: theone or more first sensors include a liquid sensor for detecting ananalyte in a liquid.
 52. The method of claim 51, wherein: the one ormore first sensors include a plurality of liquid sensors for detectingan analyte in a liquid.
 53. A sensor array for detecting an analyte in afluid, comprising: one or more substrates, each substrate having a firstsurface; one or more sensors in contact with the substrates, the sensorsbeing configured to generate a response upon exposure of the sensorarray to at least one analyte in a fluid, each sensor having a sensorvolume, the sensor volume for at least one of the sensors beingsubstantially optimized to cause the first sensor to generate anoptimized response upon exposure of the sensor array to at least onetarget analyte.
 54. The sensor array of claim 53, wherein: the sensorvolume is substantially optimized as a function of a sampling headspacevolume V_(l) and a partition coefficient K of at least one targetanalyte.
 55. The sensor array of claim 54, wherein: the sensor volumeV_(p) is substantially optimized based on the function V_(p)=V_(l)/K.56. The sensor array of claim 53, wherein: the one or more sensorsinclude two or more optimized sensors, each of the optimized sensorsbeing substantially optimized to generate an optimized response uponexposure of the sensor array to a different target analyte.
 57. Thesensor array of claim 53, wherein: the optimized response has asubstantially maximized signal to noise ratio.
 58. A sensor array fordetecting an analyte in a fluid flow, comprising: a substrate having afirst surface and a second surface; one or more sensors in contact withthe first surface, the one or more sensors being configured to generatea response upon exposure of the sensor array to at least one analyte ina fluid flow; and one or more fluid channels extending from the firstsurface to the second surface.
 59. The sensor array of claim 58,wherein: the fluid channels are configured such that upon introductionof a fluid flow to the sensor array a pressure differential is createdbetween the first and second surfaces of the substrate.
 60. The sensorarray of claim 58, wherein: the substrate includes a microporousmaterial; and the fluid channels include a plurality of pores in thesubstrate.
 61. The sensor array of claim 58, wherein: the substrateincludes an impermeable material; and the fluid channels include aplurality of holes introduced into the substrate.
 62. The sensor arrayof claim 58, wherein: the one or more sensors include a vapor sensor fordetecting an analyte in a gas.
 63. The sensor array of claim 62,wherein: the one or more sensors include a plurality of vapor sensorsfor detecting an analyte in a gas.
 64. The sensor array of claim 58,wherein: the one or more sensors include a liquid sensor for detectingan analyte in a liquid.
 65. The sensor array of claim 64, wherein: theone or more sensors include a plurality of liquid sensors for detectingan analyte in a liquid.
 66. A sensor array for detecting an analyte in afluid flow, the sensor array having a first face and a second face, thesensor array comprising: one or more substrates, each substrate forminga plate having a length, a width, and a depth, such that the length andthe width in combination define a pair of substrate faces and the widthand the depth in combination define a first substrate edge and a secondsubstrate edge, the first substrate edge for each of the substratesbeing aligned with the first face of the array; a plurality of sensorsconfigured to generate a response upon exposure of the sensor array toat least one analyte in a fluid flow, the sensors including one or morefirst sensors sensors, each of the first sensors being located along oneof the first substrate edges, the sensors also including one or moresecond sensors, each of the second sensors being located along one ofthe substrate faces; and one or more fluid channels extending along oneor more of the substrate faces from the first face of the array to thesecond face of the array.
 67. The sensor array of claim 66, wherein: theplurality of sensors includes a plurality of second sensors located atdifferent positions along at least one of the pair of substrate faces,such that the responses generated upon exposure of the sensor array toat least one analyte in a fluid flow include a spatio-temporaldifference between responses generated by each of the first and theplurality of the second sensors.
 68. The sensor array of claim 66,wherein: the sensors include a vapor sensor for detecting an analyte ina gas.
 69. The sensor array of claim 68, wherein: the sensors include aplurality of vapor sensors for detecting an analyte in a gas.
 70. Thesensor array of claim 66, wherein: the sensors include a liquid sensorfor detecting an analyte in a liquid.
 71. The sensor array of claim 70,wherein: the sensors include a plurality of liquid sensors for detectingan analyte in a liquid.
 72. A method of fabricating a sensor array fordetecting an analyte in a fluid, comprising: providing a substratehaving a surface and a sampling headspace proximate to the surface;identifying a sampling headspace volume V_(l) for at least a portion ofthe sampling headspace, and a partition coefficient K of at least onetarget analyte in a sensing material; calculating a sensor volume basedon the sampling headspace volume and the partition coefficient; andfabricating a sensor on the surface proximate to the at least a portionof the sampling headspace, the sensor including an amount of the sensingmaterial derived from the calculated sensor volume.
 73. The method ofclaim 72, wherein: the sensor volume V_(p) is calculated based on thefunction V_(p)=V_(l)/K.